Polypharmacy, functional outcome and treatment effect of intravenous alteplase for acute ischaemic stroke.

BACKGROUND AND PURPOSE: Polypharmacy is an important challenge in clinical practice. Our aim was to determine the effect of polypharmacy on functional outcome and treatment effect of alteplase in acute ischaemic stroke. METHODS: This was a post hoc analysis of the randomized, placebo-controlled WAKE-UP trial of magnetic resonance imaging guided intravenous alteplase in unknown onset stroke. Polypharmacy was defined as an intake of five or more medications at baseline. Comorbidities were assessed by the Charlson Comorbidity Index (CCI). The primary efficacy variable was favourable outcome defined by a score of 0-1 on the modified Rankin Scale at 90 days. Logistic regression analysis was used to test for an association of polypharmacy with functional outcome, and for interaction of polypharmacy and the effect of thrombolysis. RESULTS: Polypharmacy was present in 133/503 (26%) patients. Patients with polypharmacy were older (mean age 70 vs. 64 years; p < 0.0001) and had a higher score on the National Institutes of Health Stroke Scale at baseline (median 7 vs. 5; p = 0.0007). A comorbidity load defined by a CCI score ≥ 2 was more frequent in patients with polypharmacy (48% vs. 8%; p < 0.001). Polypharmacy was associated with lower odds of favourable outcome (adjusted odds ratio 0.50, 95% confidence interval 0.30-0.85; p = 0.0099), whilst the CCI score was not. Treatment with alteplase was associated with higher odds of favourable outcome in both groups, with no heterogeneity of treatment effect (test for interaction of treatment and polypharmacy, p = 0.29). CONCLUSION: In stroke patients, polypharmacy is associated with worse functional outcome after intravenous thrombolysis independent of comorbidities. However, polypharmacy does not interact with the beneficial effect of alteplase.

Efficacy of a home-based intervention programme on the physical activity level and functional ability of older people using domestic services: a randomised study.

OBJECTIVE: Our main objective was to assess whether a home-based program supervised by home helpers (HH) during their normal working hours can prevent excessive sedentariness (mainly maximum walking time and distance) and preserve functional status in elderly people at risk for frailty or disability and using domestic services. DESIGN: A four-month, open label, randomised trial with two groups called "prevention" and "control". SETTING: In the homes of study participants. PARTICIPANTS: The participants were all over 78 years old, lived independently at home, and received the visits of HHs at least once a week. INTERVENTION: The intervention combined a self-administered exercise program, with 10 g amino-acid supplementation under the supervision of HHs. MEASUREMENTS: Main outcome measures included physical activity (the PASE questionnaire), functional tests, nutritional and autonomy scores, and compliance (50% or more was considered satisfactory). Non-parametric methods were used for comparisons between the two groups. A linear regression model was fitted to assess the effect of the intervention on the relative variation of outcomes, adjusted for unbalanced baseline co-variables. RESULTS: One hundred and two persons (prevention n=53, control n=49) with a median age of 85 years were included. Their median Activities of Daily Living and Instrumental Activities of Daily Living (IADL) scores were 6 and 7 respectively. Twenty-three (44%) were good compliers for both interventions. The maximum walking time remained stable while decreasing by 25% in the control group (p=0.0015); and fewer participants had a worsened IADL score in the prevention group (p=0.05). The baseline IADL Score was significantly associated with good compliance to the prevention program (p=0.0011). In good compliers, maximum walking distance and maximum walking time increased by 29.15% (0.0 to 66.7) and 33.3% (-20.0 to 50.0) respectively. CONCLUSION: This study confirms the feasibility of a prevention program supervised by HHs, and some benefit from the intervention and identifies predictors for better compliance. It will help in the design of prevention trials for elderly people at risk for frailty.

Modelling the progression towards duodenal cancer among patients with familial polyposis on the basis of two different score profiles.

The objective was to design a method that considers, on clinical arguments, the likely existence of patient subgroups with different evolution profiles. The method is applied in familial adenomatous polyposis to predict the proportion of patients that would develop duodenal cancer. A subject-specific linear mixed-effects model was elaborated to explicitly model heterogeneity in regression parameters. The estimates of the parameters were obtained by Bayesian inference using Gibbs sampling. The application concerned two potential polyposis subgroups: stable-state and progressive. Each patient's score was expressed in function of his putative subgroup, the reference subgroup mean score (intercept), the rate of change (slope), and time. The estimated proportion of stable-state patients was 35%. In progressive-state patients, the estimated annual score increase was 0.38 (95% CI: 0.27-0.48). The regression model predicted that the proportion of patients with a score > or = 9 is near 43% at age 60 (36-50%) and 50% at 70 (43-57%). The method indicates the evolution profile of each subject, which facilitates therapeutic decisions. The modelling may be extended to other more complex situations with several subgroups, with different change rates, or with various genetic or therapeutic profiles.

A score for predicting risk of death from cardiovascular disease in adults with raised blood pressure, based on individual patient data from randomised controlled trials.

OBJECTIVE: To create a risk score for death from cardiovascular disease that can be easily used. DESIGN: Data from eight randomised controlled trials of antihypertensive treatment. SETTING: Europe and North America. PARTICIPANTS: 47 088 men and women from trials that had differing age ranges and differing eligibility criteria for blood pressure. MAIN OTUCOME MEASURE: 1639 deaths from cardiovascular causes during a mean 5.2 years of follow up. RESULTS: Baseline factors were related to risk of death from cardiovascular disease using a multivariate Cox model, adjusting for trial and treatment group (active versus control). A risk score was developed from 11 factors: age, sex, systolic blood pressure, serum total cholesterol concentration, height, serum creatinine concentration, cigarette smoking, diabetes, left ventricular hypertrophy, history of stroke, and history of myocardial infarction. The risk score is an integer, with points added for each factor according to its association with risk. Smoking contributed more in women and in younger age groups. In women total cholesterol concentration mattered less than in men, whereas diabetes had more of an effect. Antihypertensive treatment reduced the score. The five year risk of death from cardiovascular disease for scores of 10, 20, 30, 40, 50, and 60 was 0.1%, 0.3%, 0.8%, 2.3%, 6.1%, and 15.6%, respectively. Age and sex distributions of the score from the two UK trials enabled individual risk assessment to be age and sex specific. Risk prediction models are also presented for fatal coronary heart disease, fatal stroke, and all cause mortality. CONCLUSION: The risk score is an objective aid to assessing an individual's risk of cardiovascular disease, including stroke and coronary heart disease. It is useful for physicians when determining an individual's need for antihypertensive treatment and other management strategies for cardiovascular risk.