bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Prognostic Effects of Poststroke Cognitive Impairment No Dementia and Domain-Specific Cognitive Impairments in Nondisabled Ischemic Stroke Patients
Authors: Narasimhalu Kaavya , Ang Sandy , De Silva Deidre Anne , Wong Meng-Cheong , Chang Hui-Meng , Chia Kee-Seng , Auchus Alexander P. , Chen Christopher P. 
Published: February 2011

Background and Purpose—
There is some evidence that poststroke dementia, cognitive impairment no dementia (CIND), and mild cognitive impairment predict for poor outcomes such as dementia, death, and institutionalization. However, few studies have examined the prognostic value of CIND, CIND severity, and domain impairments in a poststroke cohort.

Methods—
A cohort of ischemic stroke patients with baseline cognitive assessments 3 months poststroke were followed up annually for outcomes of dependency, vascular events, and death for up to 5 years. Univariate and multivariate Cox proportional regression was performed to determine the ability CIND, CIND severity, and domain impairments to predict dependency, vascular outcomes, and death.

Results—
Four-hundred nineteen patients without dementia (mean age 60±11 years, 32% female) were followed for a mean of 3.2 years. Older age, diabetes, more severe strokes, CIND-mild, and CIND-moderate were independently predictive of dependency. There were no independent predictors of recurrent vascular events. Older age, diabetes, and CIND-moderate were independently predictive of death. In analyses of individual cognitive domains, impairments in visuomotor speed were independently predictive of dependency.

Conclusions—
In poststroke patients, CIND predicts dependency and death, while CIND severity discriminates patients with poor survival. Impairments in visuomotor speed independently predict dependency.

Clinical Trial Registration—

URL:
http://clinicaltrials.gov
. Unique Identifier: NCT00161070.
Sulfonylurea Use Before Stroke Does Not Influence Outcome
Authors: Favilla Christopher G. , Mullen Michael T. , Ali Myzoon , Higgins Peter , Kasner Scott E. 
Published: February 2011

Background and Purpose—
Sulfonylureas block nonselective cation channels and lower serum glucose and are neuroprotective in animal models of ischemic stroke. Human data on sulfonylureas in acute stroke are sparse and conflicting. We aimed to measure the potential neuroprotective effect of prestroke sulfonylurea use in diabetic patients.

Methods—
We analyzed data from a prospective cohort of individuals with diabetes mellitus (DM) enrolled in nonreperfusion ischemic stroke trials within Virtual International Stroke Trials Archive (VISTA) comprising 1050 patients, 298 with sulfonylurea use before stroke onset. The primary outcome measures were baseline National Institutes of Health Stroke Scale score and 90-day modified Rankin Scale score.

Results—
Compared with patients on no DM medications, those with sulfonylurea use before stroke onset presented with less severe stroke (OR, 0.69; 95% CI, 0.53 to 0.89) but had similar modified Rankin Scale scores at 90 days (OR, 0.95; 95% CI, 0.74 to 1.23). Compared with those on other DM agents, there was no difference in initial stroke severity (OR, 1.04; 95% CI, 0.73 to 1.48) nor modified Rankin Scale score at 90 days (OR, 1.00; 95% CI, 0.71 to 1.40). Compared with those using any DM medication, patients not on any treatment experienced higher initial National Institutes of Health Stroke Scale scores (OR, 1.48; 95% CI, 1.18 to 1.86) and were marginally more likely to have poor outcomes (modified Rankin Scale score >2) at 90 days (OR, 1.31; 95% CI, 0.97 to 1.77).

Conclusions—
Sulfonylurea use before stroke onset did not affect stroke severity or long-term functional outcome compared with other DM treatments. This finding casts doubt on the use of sulfonylureas for prophylactic neuroprotection. Furthermore, patients not using any medication for DM appear to have more severe strokes and worse outcomes.
Primary Motor Cortex in Stroke
Authors: Cirstea Carmen M. , Brooks William M. , Craciunas Sorin C. , Popescu Elena A. , Choi In-Young , Lee Phil , Bani-Ahmed Ali , Yeh Hung-Wen , Savage Cary R. , Cohen Leonardo G. , Nudo Randolph J. 
Published: February 2011

Background and Purpose—
Our goal was to investigate whether certain metabolites, specific to neurons, glial cells, or the neuronal–glial neurotransmission system, in primary motor cortices (M1), are altered and correlated with clinical motor severity in chronic stroke.

Methods—

Fourteen survivors of a single ischemic stroke located outside the M1 and 14 age-matched healthy control subjects were included. At >6 months after stroke, N-acetylaspartate,
myo
-inositol, and glutamate/glutamine were measured using proton magnetic resonance spectroscopic imaging (in-plane resolution=5×5 mm
2
) in radiologically normal-appearing gray matter of the hand representation area, identified by functional MRI, in each M1. Metabolite concentrations and analyses of metabolite correlations within M1 were determined. Relationships between metabolite concentrations and arm motor impairment were also evaluated.

Results—

The stroke survivors showed lower N-acetylaspartate and higher
myo
-inositol across ipsilesional and contralesional M1 compared with control subjects. Significant correlations between N-acetylaspartate and glutamate/glutamine were found in either M1. Ipsilesional N-acetylaspartate and glutamate/glutamine were positively correlated with arm motor impairment and contralesional N-acetylaspartate with time after stroke.

Conclusions—
Our preliminary data demonstrated significant alterations of neuronal–glial interactions in spared M1 with the ipsilesional alterations related to stroke severity and contralesional alterations to stroke duration. Thus, MR spectroscopy might be a sensitive method to quantify relevant metabolite changes after stroke and consequently increase our knowledge of the factors leading from these changes in spared motor cortex to motor impairment after stroke.
Excess Mortality and Cardiovascular Events in Patients Surviving Subarachnoid Hemorrhage
Authors: Nieuwkamp Dennis J. , Algra Ale , Blomqvist Paul , Adami Johanna , Buskens Erik , Koffijberg Hendrik , Rinkel Gabriël J.E. 
Published: February 2011

Background and Purpose—
Survivors of aneurysmal subarachnoid hemorrhage (SAH) may have an increased risk of cardiovascular events because of shared risk factors. We compared incidences of vascular diseases, vascular death, and all-cause death after SAH with those in the general population.

Methods—
From the Swedish Hospital Discharge and Cause of Death registries, we identified patients with SAH between January 1987 and January 2003. Conditional on survival of 3 months after SAH, we calculated standardized mortality and incidence ratios with corresponding 95% CIs for vascular death, all-cause death, and fatal or nonfatal vascular diseases. Cumulative risks were estimated with survival analysis.

Results—
Of 17 705 patients with SAH (mean age, 59.7 years; 59.5% women), 11 374 survived at least 3 months after SAH. During follow-up (mean, 6.8 years), 2152 (18.9%) died. The risk of death was 12.9% within 5 years, 23.6% within 10 years, and 35.4% within 15 years after SAH. The overall standardized mortality ratio was 1.57 (95% CI, 1.44 to 1.70) for vascular death and 1.61 (95% CI, 1.52 to 1.70) for all-cause death. The standardized mortality ratios were particularly high in younger individuals, ranging from 2.1 to 3.7 for vascular death and from 2.1 to 2.6 for all-cause death for patients between 50 and 65 years of age. The standardized incidence ratio for fatal or nonfatal vascular diseases was 1.51 (95% CI, 1.45 to 1.56).

Conclusions—
Mortality and risk of vascular diseases are increased in survivors of SAH. Prevention of new vascular diseases after SAH by management of risk factors seems important.
Multimodal CT-Assisted Thrombolysis in Patients With Acute Stroke
Authors: Obach Víctor , Oleaga Laura , Urra Xabier , Macho Juan , Amaro Sergio , Capurro Sebastian , Gomez-Choco Manuel , San Román Luís , Cervera Alvaro , Blasco Jordi , Vargas Martha , Torres Ferrán , Chamorro Ángel 
Published: February 2011

Background and Purpose—
The value of multimodal CT to assist thrombolysis has received little attention in stroke.

Methods—
We assessed prospectively the impact derived from the routine application of CT perfusion and CTA in patients with acute stroke treated consecutively with alteplase. The safety and efficacy of thrombolytic therapy were compared in 106 patients assisted with CT/CTA/CT perfusion (multimodal CT group) and 262 patients assisted without full multimodal brain imaging (control group) during a 5-year period (2005–2009).

Results—

Good outcome (modified Rankin scale score ≤2) at 3 months was increased in the multimodal group compared with controls (adjusted OR, 2.88; 95% CI, 1.50–5.52). Multimodal-assisted thrombolysis yielded superior benefits in patients treated beyond 3 hours (adjusted OR, 4.48; 95% CI, 1.68–11.98) than treated within 3 hours (adjusted OR, 1.31; 95% CI, 0.80–2.16; interaction test
P
=0.043). Mortality (14% and 15%) and symptomatic hemorrhage (5% and 7%) were similar in both groups.

Conclusions—
Multimodal CT use in routine clinical practice may heighten the overall efficacy of thrombolytic therapy in acute ischemic stroke. The benefits seem greater in patients treated >3 hours after stroke onset, but further randomized clinical trials are needed to confirm these findings.
The Size and Distribution of Hidden Household Income in China
Authors: Wang Xiaolu , Woo Wing Thye 
Published: February 2011

Official Chinese data on urban household income are seriously flawed because of significant underreporting of income by respondents and non-participation by the high income groups in official household surveys. We collected urban household income and expenditure data in a way that increased their reliability and the coverage of the wealthy. We utilized the well-known relationship between Engel's coefficient and income level through two different approaches to deduce the true level of household income for each of the seven Chinese income categories (lowest income, low income, lower middle income, middle income, upper middle income, high income, and highest income). We found that the ratio of our estimated income to official income increased from 1.12 for the lowest income group to 3.19 for the highest income group. Total household disposable income in 2008 is RMB 14.0 trillion according to the official data but RMB 23.2 trillion according to our estimate; and 63 percent of the unreported income went to the wealthiest 10 percent of urban households. The income of the wealthiest 10 percent of Chinese households is really 65 times that of the poorest 10 percent instead of the 23 times reported in the official data. The Gini coefficient is clearly much higher than the usually reported figure of 0.47. In one of the estimations, we had to drop the 76 wealthiest households (1.8 percent of our sample) from the analysis because there were no super-rich in the official data for us to match characteristics with. We therefore still understate the income of the highest income households. As the amount of unreported income indicates the degree of corruption, it is troubling that it grew 91 percent in 2005–08 compared to the 71 percent growth in gross national income. Serious institutional reforms must be enacted if corruption is not to derail economic development and social harmony.
Acid Mucopolysaccharides in Mammary Tumors of Dogs
Authors: Palmer T. E. , Monlux A. W. 
Published: February 2011

The predominant acid mucopolysaccharides found in selected epithelial mammary tumors of dogs stained with alcian blue and were labile to hyaluronidase digestion. These histochemical characteristics identified them as hyaluronic acid, chondroitin-4- and chondroitin-6-sulfate. The intensity of the staining of these acid mucopolysaccharides varied in a transitionary process from a precartilaginous to a pseudocartilaginous intercellular matrix to mature hyaline cartilage. The tumor acid mucopolysaccharides were indistinguishable from those associated with formation of cartilage in developing mammals; such cartilage is reported to be produced only by cells of mesodermal origin. There was no evidence to suggest transitional changes in myoepithelial cells, neoplastic epithelial cells or their components that could contribute to the formation of the acid mucopolysaccharides. It was concluded that the heterotopic tissues (cartilage, bone and fibrous connective tissue) in the epithelial mammary tumors were derived from cells of mesodermal orgin and formed the adjacent stroma in areas of neoplasia.
25-Hydroxyvitamin D is associated with plasma renin activity and the pressor response to dietary sodium intake in Caucasians
Authors: Vaidya Anand , Forman John P , Hopkins Paul N , Seely Ellen W , Williams Jonathan S 
Published: February 2011

Introduction: Concentrations of 1,25-hydroxyvitamin D have been positively associated with dietary sodium and salt sensitivity (SS) of blood pressure (BP), and inversely with plasma renin activity (PRA). We investigated the association between PRA and 25-hydroxyvitamin D (25OHD), the most clinically relevant vitamin D metabolite, and whether 25OHD associates with SS of BP in renin phenotypes of hypertension. Methods: We performed cross-sectional analyses on 223 Caucasian subjects with hypertension maintained in high and low dietary sodium balance. Subjects were distinguished as having low-renin (LR) or normal-renin (NR) hypertension. Multivariable linear regression was used to evaluate adjusted relationships. Results: Increasing 25OHD concentrations were inversely associated with PRA ( p < 0.05) on both salt diets. Furthermore, 25OHD was associated with SS of BP in LR hypertension (b = 0.62, p = 0.04), but not in NR hypertension (b = 0.06, p = 0.59). In an adjusted multivariable interaction model, renin status (LR vs . NR) was a significant effect modifier of the relationship between 25OHD and SS of BP ( p = 0.04). Conclusions: Our findings suggest that 25OHD is inversely associated with PRA and positively associated with SS of BP in LR hypertension subjects. These results extend and support prior evidence indicating an interaction between dietary sodium, the RAS, and vitamin D that influences BP in hypertension.
Comparison of dynamic block randomization and minimization in randomized trials: a simulation study
Authors: Xiao Lan , Lavori Phillip W , Wilson Sandra R , Ma Jun 
Published: February 2011

Background Minimizing the imbalance of key baseline covariates between treatments is known to be very important to the precision of the estimate of treatment effect in clinical research. Dynamic randomization allocation techniques have been used to achieve balance across multiple baseline characteristics. However, empirical data are limited on how these techniques compare in terms of balance and efficiency. We are motivated by a newly funded randomized controlled trial, in which we have the option of choosing between two methods of randomization at the subject level: (1) randomizing individual subjects consecutively as they are enrolled, using Pocock and Simon’s minimization method, and (2) simultaneously randomizing blocks of subjects once all subjects in a block have been enrolled, using a balance algorithm originally developed for cluster randomized trials. Purpose To compare dynamic block randomization and minimization in terms of balance on baseline covariates and statistical efficiency. Simple randomization was included as a reference. Methods A simulation study using data from a previous randomized controlled trial was conducted to compare balance statistics and the accuracy and power of hypothesis testing among the randomization methods. Results Dynamic block randomization consistently produced the best balance and highest power for various sample and treatment effect sizes, even after post-adjustment of the pre-specified baseline covariates in all three methods. Consistent with previous reports, minimization performed better in balance and power than simple randomization; however, the differences were noticeably smaller compared to those between dynamic block randomization and simple randomization. Limitations In this simulation study, we considered three sample sizes and two block sizes for a two-arm randomized trial. We assumed no interactions among the multiple baseline covariates. It is necessary to evaluate how the results may vary when the simulation conditions are changed before drawing broader conclusions regarding comparisons between the randomization methods. Conclusions This study demonstrates that dynamic block randomization outperforms minimization with regard to achieving balance and maximizing efficiency. Nevertheless, the differences across the three randomization strategies are modest. The statistical advantages associated with dynamic block randomization need to be considered in relation to the planned sample size and the practical issues for its implementation in deciding the preferred method of randomization for a given trial (e.g., the time required to accrue blocks of subjects of adequate size as balanced against the need to commence intervention/treatment immediately in those randomized to that experimental condition).
Likelihood inference on the relative risk in split-cluster designs
Authors: Shoukri Mohamed M , Colak Dilek , Donner Allan 
Published: February 2011

Background Split-cluster experiments are being used by investigators in health sciences when naturally occurring aggregate of individuals with nested sub-groups may be assigned to different treatments. Cited examples include the split-mouth trials, in which a subject’s mouth is divided into two segments that are randomly assigned to different treatment groups. In other situation, randomization to treatment conditions may be possible at the person level within the cluster. In this case, when the treatment conditions are available within each cluster, the design is referred to as a multisite or split-cluster design (SCD). The major attractiveness of this design is that it removes a large portion of the inter-subject variation from the estimates of the treatment effect; hence, it has the potential to require lesser number of measurements than a parallel arm design with the same power. When the response variable of interest is binary, statistical methods developed to evaluate the effect of interventions depended on nonparametric methods. Though these methods are simple to apply, they are known to be less efficient. Methods Taking the relative risk (RR) as an effect measure, we construct a bivariate-correlated model under which a score test is applied to test H0: RR = 1.0. Moreover, we construct Wald- and Fieller-based confidence intervals on RR. Since the efficiency of SCD increases when the interclass correlation coefficient (ρ12) is high, we present a goodness-of-fit procedure for testing H0:ρ12=0,  which may be helpful in choosing a design for a future study. Results For illustrating the proposed methodology, we consider two application data from the published literature; the first from a split-mouth trial on 23 patients evaluating the effect of chlorhexidine in the treatment of gingivitis, and second from study of mental health (depression and anxiety) as outcome measure obtained on 173 patients evaluated by two screening instruments. Moreover, we discussed the efficiency gained using our approach in these design settings. Limitations The likelihood approach makes more assumptions as compared to previous approaches that have been described. Conclusions We have developed a bivariate beta-binomial model, from which we can conduct a full likelihood statistical inference. Based on this model, we may construct Wald’s confidence intervals and score tests, which are known to possess optimal statistical properties. For the purpose of comparison with nonparametric methods, we constructed the Fieller’s confidence interval.
A new proposal for randomized start design to investigate disease-modifying therapies for Alzheimer disease
Authors: Zhang Richard Y , Leon Andrew C , Chuang-Stein Christy , Romano Steven J 
Published: February 2011

Background The increasing prevalence of Alzheimer disease (AD) and lack of effective agents to attenuate progression have accelerated research and development of disease modifying (DM) therapies. The traditional parallel group design and single time point analysis used in the support of past AD drug approvals address symptomatic benefit over relatively short treatment durations. More recent trials investigating disease modification are by necessity longer in duration and require larger sample sizes. Nevertheless, trial design and analysis remain mostly unchanged and may not be adequate to meet the objective of demonstrating disease modification. Randomized start design (RSD) has been proposed as an option to study DM effects, but its application in AD trials may have been hampered by certain methodological challenges. Purpose To address the methodological issues that have impeded more extensive use of RSD in AD trial and to encourage other researchers to develop novel design and analysis methodologies to better ascertain DM effects for the next generation of AD therapies, we propose a stepwise testing procedure to evaluate potential DM effects of novel AD therapies. Methods Alzheimer Disease Assessment Scale-Cognitive Subscale (ADAS-cog) is used for illustration. We propose to test three hypotheses in a stepwise sequence. The three tests pertain to treatment difference at two separate time points and a difference in the rate of change. Estimation is facilitated by the Mixed-effects Model for Repeated Measures approach. The required sample size is estimated using Monte Carlo simulations and by modeling ADAS-cog data from prior longitudinal AD studies. Results The greatest advantage of the RSD proposed in this article is its ability to critically address the question on a DM effect. The AD trial using the new approach would be longer (12-month placebo period plus 12-month delay-start period; total 24-month duration) and require more subjects (about 1000 subjects per arm for the non-inferiority margin chosen in the illustration). It would also require additional evaluations to estimate the rate of ADAS-cog change toward the end of the trial. Limitations A regulatory claim of disease modification for any compound will likely require additional verification of a drug’s effect on a validated biomarker of Alzheimer’s pathology. Conclusions Incorporation of the RSD in AD trials is feasible. With proper trial setup and statistical procedures, this design could support the detection of a disease-modifying effect. In our opinion, a two-phase RSD with a stepwise hypothesis testing procedure could be a reasonable option for future studies.