End-user perceptions of a patient- and family-centred intervention to improve nutrition intake among oncology patients: a descriptive qualitative analysis.

BACKGROUND: People with cancer are at high risk of malnutrition. Nutrition education is an effective strategy to improve patient outcomes, however, little is known regarding the impact of family and/or carer involvement in nutrition education and requires investigation. The purpose of the study was to evaluate PIcNIC (Partnering with families to promote nutrition in cancer care) intervention acceptability from the perspective of patients, families and health care providers. METHODS: A descriptive qualitative study was undertaken at an inpatient and an outpatient hospital setting in Australia and an outpatient/home setting in Hong Kong. A patient-and-family centred intervention including nutrition education, goals setting/nutrition plans, and food diaries, was delivered to patients and/or families in the inpatient, outpatient or home setting. Semi-structured interviews were used to explore perceptions of the intervention. 64 participants were interviewed; 20 patients, 15 family members, and 29 health care professionals. Data were analysed using deductive and inductive content analysis. RESULTS: Two categories were identified; 1) 'context and intervention acceptability'; and 2) 'benefits of patient- and family-centred nutrition care'. Within each category redundant concepts were identified. For category 1 the redundant concepts were: the intervention works in outpatient settings, the food diary is easy but needs to be tailored, the information booklet is a good resource, and the intervention should be delivered by a dietitian, but could be delivered by a nurse. The redundant concepts for category 2 were: a personalised nutrition plan is required, patient and family involvement in the intervention is valued and the intervention has benefits for patients and families. Converging and diverging perceptions across participant groups and settings were identified. CONCLUSIONS: In this paper we have described an acceptable patient- and family-centred nutrition intervention, which may be effective in increasing patient and family engagement in nutrition care and may result in improved nutrition intakes. Our study highlights important contextual considerations for nutrition education; the outpatient and home setting are optimal for engaging patients and families in learning opportunities.

Mortality in intensive care: The impact of bacteremia and the utility of systemic inflammatory response syndrome.

BACKGROUND: The purpose of this study was to determine the impact of bacteremia on intensive care unit (ICU) mortality and to develop a bacteremia prediction tool using systemic inflammatory response syndrome (SIRS) criteria. METHODS: Patients included those aged >18 years who had blood cultures taken in the ICU from January 1, 2011-December 31, 2013. Eligible patients were identified from microbiology records of the Glasgow Royal Infirmary, Scotland. Clinical and outcome data were gathered from ICU records. Patients with clinically significant bacteremia were matched to controls using propensity scores. SIRS criteria were gathered and used to create decision rules to predict the absence of bacteremia. The main outcome was mortality at ICU discharge. The utility of the decision tools was measured using sensitivity and specificity. RESULTS: One hundred patients had a clinically significant positive blood culture and were matched to 100 controls. Patients with bacteremia had higher ICU mortality (odds ratio [OR], 2.35; P = .001) and longer ICU stay (OR, 17.0 vs 7.8 days; P ≤ .001). Of 1,548 blood culture episodes, 1,274 met ≥2 SIRS criteria (106 significant positive cultures and 1,168 negative cultures). There was no association between SIRS criteria and positive blood cultures (P = .11). A decision rule using 3 SIRS criteria had optimal predictive performance (sensitivity, 56%; specificity, 50%) but low accuracy. CONCLUSIONS: ICU patients with bacteremia have increased mortality and length of ICU stay. SIRS criteria cannot be used to identify patients at low risk of bacteremia.

National Institutes of Health Stroke Scale Item Profiles as Predictor of Patient Outcome: External Validation on Safe Implementation of Thrombolysis in Stroke-Monitoring Study Data.

BACKGROUND AND PURPOSE: National Institutes of Health Stroke Scale (NIHSS) item profiles that were recently proposed and validated may prove useful for clinical prognostication and research studies. We aimed to validate the NIHSS item profiles in hyper-acute stroke patients who received thrombolysis treatment (tissue-type plasminogen activator). METHODS: We applied the latent class analysis probabilities of the profile membership generated from the derivation study onto NIHSS data from the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST). We separately considered NIHSS data collected within 3 hours and at ≈24 hours after stroke onset to obtain 2 sets of symptom groupings. The discrimination and calibration of both sets of symptom profiles were assessed from their association with outcomes. The outcome measures included modified Rankin Scale (mRS; using full distribution and dichotomized, mRS 0-1 or back to baseline) at day 90 and mortality by 90 days. RESULTS: We obtained data for 6843 patients. Ordinal analysis of mRS showed odds of better outcome across the profiles, for each set of symptom profiles, adjusted for age, sex, and prestroke mRS. Dichotomized outcomes mirrored the ordinal findings. There were significant differences in prognostic discrimination ability for the dichotomized outcome measures between the 2 sets of symptom profiles, with the latter set (ie, 24-hour symptom profiles) performing better. CONCLUSIONS: The NIHSS item profiles are individually associated with functional outcome and mortality in acute stroke patients treated with tissue-type plasminogen activator. Considering profiles of NIHSS subscores rather than only the total score is informative for prognostication, particularly for assessments collected 24 hours after stroke onset.

Risk Factors of Ischemic Stroke and Subsequent Outcome in Patients Receiving Hemodialysis.

BACKGROUND AND PURPOSE: End-stage renal disease (ESRD) requiring hemodialysis carries up to a 10-fold greater risk of stroke than normal renal function. Knowledge on risk factors and management strategies derived from the general population may not be applicable to those with ESRD. We studied a large ESRD population to identify risk factors and outcomes for stroke. METHODS: All adult patients receiving hemodialysis for ESRD from January 1, 2007, to December 31, 2012, were extracted from the electronic patient record. Variables associated with stroke were identified by survival analysis; demographic, clinical, imaging, and dialysis-related variables were assessed, and case-fatality was determined. Follow-up was until December 31, 2013. RESULTS: A total of 1382 patients were identified (mean age, 60.5 years; 58.5% men). The prevalence of atrial fibrillation was 21.2%, and 59.4% were incident hemodialysis patients. One hundred and sixty patients (11.6%) experienced a stroke during 3471 patient-years of follow-up (95% ischemic). Stroke incidence was 41.5/1000 patient-years in prevalent and 50.1/1000 patient-years in incident hemodialysis patients. Factors associated with stroke on regression analysis were prior stroke, diabetes mellitus, and age at starting renal replacement therapy. Atrial fibrillation was not significantly associated with stroke, and warfarin did not affect stroke risk in warfarin-treated patients. Fatality was 18.8% at 7 days, 26.9% at 28 days, and 56.3% at 365 days after stroke. CONCLUSIONS: Incidence of stroke is high in patients with ESRD on hemodialysis with high case-fatality. Incident hemodialysis patients had the highest stroke incidence. Many, but not all, important risk factors commonly associated with stroke in the general population were not associated with stroke in patients receiving hemodialysis.

Risk of Stroke in Chronic Heart Failure Patients Without Atrial Fibrillation: Analysis of the Controlled Rosuvastatin in Multinational Trial Heart Failure (CORONA) and the Gruppo Italiano per lo Studio della Sopravvivenza nell'Insufficienza Cardiaca-Heart Failure (GISSI-HF) Trials.

BACKGROUND: Our aim was to describe the incidence and predictors of stroke in patients who have heart failure without atrial fibrillation (AF). METHODS AND RESULTS: We pooled 2 contemporary heart failure trials, the Controlled Rosuvastatin in Multinational Trial Heart Failure (CORONA) and the Gruppo Italiano per lo Studio della Sopravvivenza nell'Insufficienza cardiaca-Heart Failure trial (GISSI-HF). Of the 9585 total patients, 6054 did not have AF. Stroke occurred in 165 patients (4.7%) with AF and in 206 patients (3.4%) without AF (rates 16.8/1000 patient-years and 11.1/1000 patient-years, respectively). Using Cox proportional-hazards models, we identified the following independent predictors of stroke in patients without AF (ranked by χ(2) value): age (hazard ratio, 1.34; 95% confidence interval, 1.18-1.63 per 10 years), New York Heart Association class (1.60, 1.21-2.12 class III/IV versus II), diabetes mellitus treated with insulin (1.87, 1.22-2.88), body mass index (0.74, 0.60-0.91 per 5 kg/m(2) up to 30), and previous stroke (1.81, 1.19-2.74). N-terminal pro B-type natriuretic peptide (available in 2632 patients) was also an independent predictor of stroke (hazard ratio, 1.31; 1.11-1.57 per log unit) when added to this model. With the use of a risk score formulated from these predictors, we found that patients in the upper third of risk had a rate of stroke that approximated the risk in patients with AF. CONCLUSIONS: A small number of demographic and clinical variables identified a subset of patients who have heart failure without AF at a high risk of stroke.

Acetaminophen use and risk of myocardial infarction and stroke in a hypertensive cohort.

Recent data suggest that self-reported acetaminophen use is associated with increased risk of cardiovascular events and that acetaminophen causes a modest blood pressure rise. There are no randomized trials or studies using verified prescription data of this relationship. We aimed to assess the relationship between verified acetaminophen prescription data and risk of myocardial infarction or stroke in patients with hypertension. We performed a retrospective data analysis using information contained within the UK Clinical Research Practice Datalink. Multivariable Cox proportional hazard models were used to estimate hazard ratios for myocardial infarction (primary end point), stroke, and any cardiovascular event (secondary end points) associated with acetaminophen use during a 10-year period. Acetaminophen exposure was a time-dependent variable. A propensity-matched design was also used to reduce potential for confounding. We included 24,496 hypertensive individuals aged ≥ 65 years. Of these, 10,878 were acetaminophen-exposed and 13,618 were not. There was no relationship between risk of myocardial infarction, stroke, or any cardiovascular event and acetaminophen exposure on adjusted analysis (hazard ratio, 0.98; 95% confidence interval, 0.76-1.27; hazard ratio, 1.09; 95% confidence interval, 0.86-1.38; and hazard ratio, 1.17; 95% confidence interval, 0.99-1.37; respectively). Results in the propensity-matched sample (n=4000 per group) and when men and women were analyzed separately were similar. High-frequency users (defined as receiving a prescription for >75% of months) were also not at increased risk. After allowance for potentially confounding variables, the use of acetaminophen was not associated with an increased risk of myocardial infarction or stroke in a large cohort of hypertensive patients.

Selection for delayed intravenous alteplase treatment based on a prognostic score.

BACKGROUND AND PURPOSE: Approved use of intravenous alteplase for ischemic stroke offers net benefit. Pooled randomized controlled trial analysis suggests additional patients could benefit but others be harmed with treatment initiated beyond 4·5 h after stroke onset. We proposed prognostic scoring methods to identify a strategy for patient selection. METHODS: We selected 500 patients treated by intravenous alteplase and 500 controls from Virtual International Stroke Trials Archive, matching modified Rankin score outcomes to those from pooled randomized controlled trial 4·5-6 h data. We ranked patients by prognostic score. We chose limits to optimize our sample for a net treatment benefit significant at P = 0·01 by Cochran-Mantel-Haenszel test and by ordinal regression. For validation, we had these applied to the pooled randomized controlled trial data for 4·5-6 h, testing for net benefit by Cochran-Mantel-Haenszel test, ordinal regression, and also by dichotomized outcomes: modified Rankin score 0-1, mortality and parenchymal hemorrhage type 2 bleeds. All analyses were adjusted for age and National Institutes of Health Stroke Scale. RESULTS: In the training dataset, limits of 56-95 on a prognostic score retained 714 patients in whom there was net benefit significant at P = 0·01. When applied to the 1120 patients in the pooled randomized controlled trial 4·5-6 h dataset, score limits of 56-95 retained 711 patients and gave odds ratio for improved modified Rankin score distribution of 1·13, 95% confidence interval 0·87-1·47, Cochran-Mantel-Haenszel P = 0·89. More patients achieved modified Rankin score 0-1 (odds ratio 1·44, 1·02-2·05, P = 0·04) but mortality and parenchymal hemorrhage type 2 bleeds were increased: odds ratio 1·56, 1·01-2·40, P = 0·04; odds ratio 15·6, 3·7-65·8, P = 0·0002, respectively. CONCLUSION: Selection of patients between 4·5 and 6 h based on simple clinical measures failed to deliver a population in whom the alteplase effect would be safe and effective.

National institutes of health stroke scale item profiles as predictor of patient outcome: external validation on independent trial data.

BACKGROUND AND PURPOSE: National Institutes of Health Stroke Scale (NIHSS) item profiles that were recently proposed may prove useful both clinically and for research studies. We aimed to validate the NIHSS item profiles in an acute cohort. METHODS: We conducted a retrospective analysis on pooled data from randomized clinical trials. We applied the latent class analysis probabilities of profile membership developed from the derivation study to obtain symptom grouping, a-NIHSS item profiles. We implemented an independent latent class analysis to derive secondary symptom grouping, b-NIHSS item profiles. Validation was performed by assessing the associations with outcomes and evaluating both sets of NIHSS item profiles' discrimination and calibration to the data. The outcomes evaluated included modified Rankin Scale (mRS; using the full distribution and dichotomized, mRS, 0-1) at day 90 and mortality by 90 days. RESULTS: We identified 10 271 patients. Ordinal analysis of mRS confirmed increased odds of better outcome across the profiles in a stepwise manner, adjusted for age and thrombolysis treatment, for each set of NIHSS item profiles. Similar patterns were observed for mRS 0 to 1, and inverse patterns were seen for mortality. The c-statistics of a-NIHSS and b-NIHSS item profiles for mRS 0 to 1 were similar at 0.71 (95% confidence interval, 0.70-0.72) and for mortality, 0.74 (0.73-0.75) and 0.75 (0.73-0.76), respectively. Calibration was good. CONCLUSIONS: These NIHSS item profiles identified using latent class analysis offer a reliable approach to capture the true response patterns that are associated with functional and outcome and mortality post stroke. This approach has the potential to enhance the clinical value of the overall NIHSS score.

Transcranial laser therapy in acute stroke treatment: results of neurothera effectiveness and safety trial 3, a phase III clinical end point device trial.

BACKGROUND AND PURPOSE: On the basis of phase II trials, we considered that transcranial laser therapy could have neuroprotective effects in patients with acute ischemic stroke. METHODS: We studied transcranial laser therapy in a double-blind, sham-controlled randomized clinical trial intended to enroll 1000 patients with acute ischemic stroke treated ≤24 hours after stroke onset and who did not undergo thrombolytic therapy. The primary efficacy measure was the 90-day functional outcome as assessed by the modified Rankin Scale, with hierarchical Bayesian analysis incorporating relevant previous data. Interim analyses were planned after 300 and 600 patients included. RESULTS: The study was terminated on recommendation by the Data Monitoring Committee after a futility analysis of 566 completed patients found no difference in the primary end point (transcranial laser therapy 140/282 [49.6%] versus sham 140/284 [49.3%] for good functional outcome; modified Rankin Scale, 0-2). The results remained stable after inclusion of all 630 randomized patients (adjusted odds ratio, 1.024; 95% confidence interval, 0.705-1.488). CONCLUSIONS: Once the results of the interim futility analysis became available, all study support was immediately withdrawn by the capital firms behind PhotoThera, and the company was dissolved. Proper termination of the trial was difficult but was finally achieved through special efforts by former employees of PhotoThera, the CRO Parexel and members of the steering and the safety committees. We conclude that transcranial laser therapy does not have a measurable neuroprotective effect in patients with acute ischemic stroke when applied within 24 hours after stroke onset. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01120301.

Characteristic adverse events and their incidence among patients participating in acute ischemic stroke trials.

BACKGROUND AND PURPOSE: Adverse events (AE) in trial populations present a major burden to researchers and patients, yet most events are unrelated to investigational treatment. We aimed to develop a coherent list of expected AEs, whose incidence can be predicted by patient characteristics that will inform future trials and perhaps general poststroke care. METHODS: We analyzed raw AE data from patients participating in acute ischemic stroke trials. We identified events that occurred with a lower 99% confidence bound greater than nil. Among these, we applied receiver operating characteristic principles to select the fewest types of events that together represented the greatest number of reports. Using ordinal logistic regression, we modeled the incidence of these events as a function of patient age, sex, baseline National Institutes of Health Stroke Scale, and multimorbidity status, defining P<0.05 as statistically significant. RESULTS: We analyzed 5775 placebo-treated patients, reporting 21 217 AEs. Among 756 types of AEs, 132 accounted for 82.7%, of which 80% began within 10 days after stroke. Right hemisphere (odds ratio [OR], 1.67), increasing baseline National Institutes of Health Stroke Scale (OR, 1.11), multimorbidity status (OR, 1.09 per disease), patient age (OR, 1.01 per year), height (OR, 1.01 per centimeter), diastolic blood pressure (OR, 0.99 per mm Hg), and smoking (OR, 0.82) were independently associated with developing more AEs but together explained only 13% of the variation. CONCLUSIONS: A list of 132 expected AEs after acute ischemic stroke may be used to simplify interpretation and reporting of complications. AEs can be modestly predicted by patient characteristics, facilitating stratification of patients by risk for poststroke complications.

Allopurinol initiation and change in blood pressure in older adults with hypertension.

Hypertension is a key risk factor for cardiovascular disease, and new treatments are needed. Uric acid reduction lowers blood pressure (BP) in adolescents, suggesting a direct pathophysiological role in the development of hypertension. Whether the same relationship is present in older adults is unknown. We explored change in BP after allopurinol initiation using data from the UK Clinical Practice Research Datalink. Data were extracted for patients with hypertension aged >65 years who were prescribed allopurinol with pretreatment and during treatment BP readings. Data from comparable controls were extracted. The change in BP in patients with stable BP medication was the primary outcome and was compared between groups. Regression analysis was used to adjust for potential confounding factors, and a propensity-matched sample was generated. Three hundred sixty-five patients who received allopurinol and 6678 controls were included. BP fell in the allopurinol group compared with controls (between-group difference in systolic and diastolic BP: 2.1 mm Hg; 95% confidence interval, -0.6 to 4.8; and 1.7 mm Hg; 95% confidence interval, 0.4-3.1, respectively). Allopurinol use was independently associated with a fall in both systolic and diastolic BP on regression analysis (P<0.001). Results were consistent in the propensity-matched sample. There was a trend toward greater fall in BP in the high-dose allopurinol group, but change in BP was not related to baseline uric acid level. Allopurinol use is associated with a small fall in BP in adults. Further studies of the effect of high-dose allopurinol in adults with hypertension are needed.

The effect of time to treatment on outcome in very elderly thrombolysed stroke patients.

BACKGROUND: Intravenous thrombolysis is beneficial in, even very elderly, acute ischemic stroke patients. However, while the relation between treatment benefit and treatment delay (onset time to treatment) in patients younger than 80 years is well known, it is uncertain in the very elderly. AIMS: This analysis aims at examining this relationship in the elderly, and to provide a comparison with the derived relationship in younger patients as a check of validity. METHODS: We assessed the interaction between age, onset time to treatment, and thrombolysis exposure by analyzing the modified Rankin scale score distribution or mortality rate at 90 days, among patients registered in a trials archive. We established whether the effect of alteplase changes with onset time to treatment, by treating onset time to treatment as a continuum in a multivariate logistic regression model. RESULTS: Data were available for 3063 patients, of whom 2341 were thrombolysed. Five hundred ninety-seven patients were aged >80, of whom 352 were thrombolysed. Among patients aged >80, no significant interaction of outcome with onset time to treatment was observed (P = 0·4650), but the estimated slope of the decay in benefit with onset time to treatment was comparable with that established for younger patients. Analyzing the entire dataset, there was an interaction between onset time to treatment and alteplase treatment (P = 0·0159), but neither between age and onset time to treatment (P = 0·7098) nor between age and alteplase treatment (P = 0·0755). CONCLUSIONS: In this nonrandomized comparison, the relationship of benefit and safety with thrombolysis across onset time to treatment in very elderly stroke patients was comparable with that in their younger counterparts. Across the investigated time span of 3·5 h, we can safely treat with the same time window as we use for younger patients.

Intracluster correlation coefficients and reliability of randomized multicenter stroke trials within VISTA.

BACKGROUND: Reliable estimates of intracluster correlation coefficients (ICCs) for specific outcome measures are crucial for sample size calculations of future cluster randomized trials. ICCs indicate the proportion of data variability that is explained by defined levels of clustering. AIMS: In this manuscript, we present potentially valuable and reliable estimates of ICCs for specific baseline and follow-up data. METHOD: ICCs were estimated from linear and generalized linear mixed models using maximum likelihood estimation for common measures used in stroke research, including modified Rankin Scale (mRS), National Institutes of Health Stroke Scale (NIHSS), and Barthel Index (BI). RESULTS: Data were available for 11 841 patients with ischemic stroke from 11 randomized trials. After adjusting for age, thrombolysis, and baseline NIHSS, the median ICC for follow-up data, using center as the level of clustering, ranged from 0·007 to 0·041. The ICCs using trial, continent or year of enrollment as level of clustering were distinctly lower. Less than 1% of the variability of mRS, NIHSS, and BI was explained by any of these three cluster levels. CONCLUSION: This compendium of relevant ICC estimates should assist trial planning. For example, the sample size for a cluster trial with 150 patients per center using ordinal analysis of mRS should be inflated by 2·0 due to the ICC of 0·007; whereas the ICC of 0·031 using mRS dichotomized above mRS 0-1, requires inflation by 5·6. The low contribution of trials, year or continent of enrollment to overall variation in outcome offers reassurance that analyses using pooled data from multiple trials in VISTA are unlikely to suffer from bias from these sources.

Exploration of time-course combinations of outcome scales for use in a global test of stroke recovery.

BACKGROUND: Clinical trials for acute ischemic stroke treatment require large numbers of participants and are expensive to conduct. Methods that enhance statistical power are therefore desirable. AIMS: We explored whether this can be achieved by a measure incorporating both early and late measures of outcome (e.g. seven-day NIH Stroke Scale combined with 90-day modified Rankin scale). METHODS: We analyzed sensitivity to treatment effect, using proportional odds logistic regression for ordinal scales and generalized estimating equation method for global outcomes, with all analyses adjusted for baseline severity and age. We ran simulations to assess relations between sample size and power for ordinal scales and corresponding global outcomes. We used R version 2·12·1 (R Development Core Team. R Foundation for Statistical Computing, Vienna, Austria) for simulations and SAS 9·2 (SAS Institute Inc., Cary, NC, USA) for all other analyses. RESULTS: Each scale considered for combination was sensitive to treatment effect in isolation. The mRS90 and NIHSS90 had adjusted odds ratio of 1·56 and 1·62, respectively. Adjusted odds ratio for global outcomes of the combination of mRS90 with NIHSS7 and NIHSS90 with NIHSS7 were 1·69 and 1·73, respectively. The smallest sample sizes required to generate statistical power ≥80% for mRS90, NIHSS7, and global outcomes of mRS90 and NIHSS7 combined and NIHSS90 and NIHSS7 combined were 500, 490, 400, and 380, respectively. DISCUSSION: When data concerning both early and late outcomes are combined into a global measure, there is increased sensitivity to treatment effect compared with solitary ordinal scales. This delivers a 20% reduction in required sample size at 80% power. Combining early with late outcomes merits further consideration.

Impact of benzodiazepines on functional outcome and occurrence of pneumonia in stroke: evidence from VISTA.

BACKGROUND: Benzodiazepines have been proposed both as a neuroprotectant and risk factor for pneumonia in acute stroke. AIMS: We assessed the impact of benzodiazepine exposure on the modified Rankin scale score distribution at 90 days as well as pneumonia rates among patients registered in a trials archive. METHOD: We used an age, baseline National Institutes of Health Stroke Score, and thrombolysis-rate adjusted Cochran-Mantel-Haenszel test to test significance (P) followed by proportional odds logistic regression analysis to estimate the odds ratios for improved modified Rankin scale score, and binary logistic regression to estimate the odds ratio for developing pneumonia. RESULTS: Data were available for 5938 patients, of whom 1800 received benzodiazepines. No association of benzodiazepine use and overall stroke outcome could be found (odds ratio 0·90, 95% confidence interval 0·82-1·00, P=0·121). Pneumonia occurred in 12·8% of patients treated with benzodiazepines and in 13·6% of the controls (odds ratio 0·99, 95% confidence interval 0·83-1·18, P=0·904). CONCLUSION: In this nonrandomized comparison, treatment with benzodiazepines as a concomitant medication had no independent impact on stroke outcome.

How well do standard stroke outcome measures reflect quality of life? A retrospective analysis of clinical trial data.

BACKGROUND AND PURPOSE: Quality of life (QoL) is important to stroke survivors yet is often recorded as a secondary measure in acute stroke randomized controlled trials. We examined whether commonly used stroke outcome measures captured aspects of QoL. METHODS: We examined primary outcomes by National Institutes of Health Stroke Scale (NIHSS), Barthel Index (BI) and modified Rankin Scale (mRS), and QoL by Stroke Impact Scale (SIS) and European Quality of Life Scale (EQ-5D) from the Virtual International Stroke Trials Archive (VISTA). Using Spearman correlations and logistic regression, we described the relationships between QoL mRS, NIHSS, and BI at 3 months, stratified by respondent (patient or proxy). Using χ2 analyses, we examined the mismatch between good primary outcome (mRS ≤1, NIHSS ≤5, or BI ≥95) but poor QoL, and poor primary outcome (mRS ≥3, NIHSS ≥20, or BI ≤60) but good QoL. RESULTS: Patient-assessed QoL had a stronger association with mRS (EQ-5D weighted score n=2987, P<0.0001, r=-0.7, r2=0.53; SIS recovery n=2970, P<0.0001, r=-0.71, r2=0.52). Proxy responses had a stronger association with BI (EQ-5D weighted score n=837, P<0.0001, r=0.78, r2=0.63; SIS recovery n=867, P<0.0001, r=0.68, r2=0.48). mRS explained more of the variation in QoL (EQ-5D weighted score=53%, recovery by SIS v3.0=52%) than NIHSS or BI and resulted in fewer mismatches between good primary outcome and poor QoL (P<0.0001, EQ-5D weighted score=8.5%; SIS recovery=10%; SIS-16=4.4%). CONCLUSIONS: The mRS seemed to align closely with stroke survivors' interests, capturing more information on QoL than either NIHSS or BI. This further supports its recommendation as a primary outcome measure in acute stroke randomized controlled trials.

Acetaminophen use and change in blood pressure in a hypertensive population.

OBJECTIVE: Recent data suggest that self-reported acetaminophen use is associated with increased risk of cardiovascular events and a rise in arterial blood pressure (BP). We investigated the association between acetaminophen use and BP in a large cohort of patients with hypertension using verified prescription data. METHODS: We extracted data from the UK General Practice Research Database for all hypertensive patients aged 65 years or older who were prescribed acetaminophen and had BP measured both before and during acetaminophen treatment. Patients were grouped according to whether their antihypertensive treatment remained unchanged or not during the study period. The change in SBP and DBP during acetaminophen use was determined and compared with the change in BP in a group of nonacetaminophen-exposed people identified using propensity matching. RESULTS: A total of 2754 acetaminophen-exposed individuals were included. BP rose slightly during the period of acetaminophen treatment wherein antihypertensive treatment was unchanged [change in SBP 1.6 [95% confidence interval (CI) 0.7-2.5) mmHg and change in DBP 0.5 (95% CI 0.1-1.0) mmHg)]. BP fell when new antihypertensive medications were prescribed. These BP changes were no different to those seen in matched nonacetaminophen-exposed individuals [between-group difference wherein antihypertensive treatment was unchanged was 0.6 (95% CI -0.6 to 1.9) mmHg and 0.5 (-0.1 to 1.1) mmHg for change in SBP and DBP, respectively]. CONCLUSION: We found no evidence of a sustained rise in blood pressure caused by acetaminophen treatment in a large population of patients with treated hypertension.

Does the cognitive measure Cog-4 show improvement among patients treated with thrombolysis after acute stroke?

BACKGROUND: Although the established measure of disability post stroke, the modified Rankin Scale emphasizes motor function and may underestimate the importance of cognitive impairment in more disabled patients. A subset of four items from the National Institutes of Health Stroke Scale has been proposed to assess cognitive function after stroke (Cog-4), and to correlate with modified Rankin Scale. Items correspond to orientation, executive function, language, and inattention. We investigated responsiveness of Cog-4 to treatment with thrombolysis and whether it offers information that supplements modified Rankin Scale. METHODS: We included 6268 patients from the Virtual International Stroke Trials Archive: 2734 received intravenous thrombolysis and 3534 were treated conservatively. We compared day 90 outcomes between treated and untreated groups, by modified Rankin Scale (illustrative) and by Cog-4 (primary measure) adjusting for age, baseline National Institutes of Health stroke scale, hemispheric lateralisation as well as baseline Cog-4 and baseline National Institutes of Health Stroke Scale excluding baseline Cog-4 separately. Analysis of Cog-4 was repeated within strata of 90 day modified Rankin Scale. Statistical analyses included proportional odds logistic regression and Cochran-Mantel-Haenszel test. RESULTS: Modified Rankin Scale showed a difference between treatment groups of expected magnitude (odds ratio 1·56; 95% confidence interval 1·43-1·72; P < 0·001). After adjustment for imbalance in baseline prognostic factors, the distribution of Cog-4 scores at 90 days was better in thrombolysed patients compared with nonthrombolysed patients (odds ratio 1·31; 95% confidence interval 1·18-1·47; P = 0·006). However, Cog-4 analysis stratified by 90-day modified Rankin Scale was neutral between treatment groups (OR 1·01; 95% CI 0·90-1·14), and Cog-4 was not responsive to treatment group even within modified Rankin Scale categories 4 and 5 despite substantial cognitive deficits in these patients. CONCLUSION: Although Cog-4 may be responsive to treatment effects, it does not provide additional information beyond modified Rankin Scale assessment.

Impact of atrial fibrillation on outcome in thrombolyzed patients with stroke: evidence from the Virtual International Stroke Trials Archive (VISTA).

BACKGROUND AND PURPOSE: Atrial fibrillation has been considered a risk factor for poor outcome from acute stroke and may influence response to thrombolysis, although supporting data are limited due to potential confounding with age and stroke severity. METHOD: We assessed the association of atrial fibrillation and thrombolysis exposure with the modified Rankin Scale score distribution at 90 days among patients registered in a trials archive. We used an age and baseline National Institutes of Health Stroke Scale-adjusted Cochran-Mantel-Haenszel test to test significance (P) followed by proportional odds logistic regression analysis to estimate the ORs for improved modified Rankin Scale score. RESULTS: Data were available for 7091 patients, of whom 3027 were thrombolyzed. A total of 1631 patients had a history of atrial fibrillation, of whom 639 were thrombolyzed. Among patients with atrial fibrillation, baseline severity was greater (median baseline National Institutes of Health Stroke Scale, 14 versus 12; P<0.001) and age was higher (mean age, 74.0 versus 66.5; P<0.001). An association of treatment with outcome was seen independently and was of similar magnitude within patients with atrial fibrillation (OR, 1.44; 95% CI, 1.12-1.73; P<0.001) and without atrial fibrillation (OR, 1.53; 95% CI, 1.39-1.69; P<0.001). No association of atrial fibrillation and overall stroke outcome could be found (OR, 0.93; 95% CI, 0.84-1.03; P=0.409). CONCLUSIONS: In this nonrandomized comparison, presence of atrial fibrillation had no independent impact on stroke outcome and compared with untreated comparators, the patients who received thrombolysis experienced an advantage in outcomes that was of equal magnitude whether in the presence or absence of atrial fibrillation.