Biomedical subjects

Rema Raman

Publications and source records attributed to Rema Raman.

13 recordsLinked to original sources

PubMed2006

An expedited code stroke protocol is feasible and safe.

BACKGROUND AND PURPOSE: Stroke recovery critically depends on timely reperfusion. In July 2003, we set a benchmark onset-to-treatment time of < or =2 hours and instituted an expedited code stroke protocol to accomplish this. We aim to show that the protocol is feasible and safe. METHODS: The expedited protocol includes: Benchmark onset-to-treatment within 2 hours; in-person triage of all code stroke patients; unmixed tissue plasminogen activator at the bedside during evaluation; no delays pending coagulation tests, chest x-ray, or stool guiac unless specifically indicated; and no delays pending formal CT interpretation or written consent. RESULTS: Between July 2003 and June 2005, we evaluated 781 patients and treated 103 of 781 (13.2%) with intravenous recombinant tissue plasminogen activator within 3 hours. Of these, we treated 49 of 103 (47.6%) within 2 hours of symptom onset, and 54 of 103 (52.4%) between 2 and 3 hours. The overall risk of symptomatic intracerebral hemorrhage was 4 of 103 (3.9%; 95% CI, 1.1%, 9.6%), and not significantly different from 6.4% (P=0.42). The hemorrhage risks in those treated within 2 hours of symptom onset and those treated between 2 and 3 hours were not significantly different from each other or from 6.4%. CONCLUSIONS: The expedited code stroke protocol is feasible and appears safe. Further study is warranted to confirm its safety and determine whether it results in better clinical outcomes.

Adult↗

PubMed2005

A mixed-effects regression model for three-level ordinal response data.

Three-level data occur frequently in behaviour and medical sciences. For example, in a multi-centre trial, subjects within a given site are randomly assigned to treatments and then studied over time. In this example, the repeated observations (level-1) are nested within subjects (level-2) who are nested within sites (level-3). Similarly, in twin studies, repeated measurements (level-1) are taken on each twin (level-2) within each twin pair (level-3). A three-level mixed-effects regression model is described here. Random effects at the second and third level are included in the model. Additionally, both proportional odds and non-proportional odds models are developed. The latter allows the effects of explanatory variables to vary across the cumulative logits of the model. A maximum marginal likelihood (MML) solution is described and Gauss-Hermite numerical quadrature is used to integrate over the distribution of random effects. The random effects are normally distributed in this instance. Features of this model are illustrated using data from a school-based smoking prevention trial and an Alzheimer's disease clinical trial.

Alzheimer Disease↗

PubMed2005

NIHSS training and certification using a new digital video disk is reliable.

BACKGROUND AND PURPOSE: NIH Stroke Scale certification is required for participation in modern stroke clinical trials and as part of good clinical care in stroke centers. The existing training and certification videotapes, however, are more than 10 years old and do not contain an adequate balance of patient findings. METHODS: After producing a new NIHSS training and demonstration DVD, we selected 18 patients representing all possible scores on 15 scale items for a new certification DVD. Patients were divided into 3 certification groups of 6 patients each, balanced for lesion side, distribution of scale item findings, and total score. We sought to measure interrater reliability of the certification DVD using methodology previously published for the original videotapes. Raters were recruited from 3 experienced stroke centers. Each rater watched the new training DVD and then evaluated one of the 3 certification groups. RESULTS: Responses were received from 112 raters: 26.2% of all responses came from stroke nurses, 34.1% from emergency departments/other physicians, and 39.6% from neurologists. One half (50%) of raters were previously NIHSS-certified. Item responses were tabulated, scoring performed as previously published, and agreement measured with unweighted kappa coefficients for individual items and an intraclass correlation coefficient for the overall score. kappa ranged from 0.21+/-0.05 (ataxia) to 0.92+/-0.09 (LOC-C questions). Of 15 items, 2 showed poor, 11 moderate, and 2 excellent agreement based on kappa scores. The intraclass correlation coefficient for total score was 0.94 (95% confidence interval, 0.84 to 1.00). Reliability scores were similar among specialists and centers, and there were no differences between nurses and physicians. kappa scores trended higher among raters previously certified. CONCLUSIONS: These certification DVDs are reliable for NIHSS certification, and scoring sheets have been posted on a web site for real-time, online certification.

Cerebrovascular Disorders↗

PubMed2005

Axonopathy and transport deficits early in the pathogenesis of Alzheimer's disease.

We identified axonal defects in mouse models of Alzheimer's disease that preceded known disease-related pathology by more than a year; we observed similar axonal defects in the early stages of Alzheimer's disease in humans. Axonal defects consisted of swellings that accumulated abnormal amounts of microtubule-associated and molecular motor proteins, organelles, and vesicles. Impairing axonal transport by reducing the dosage of a kinesin molecular motor protein enhanced the frequency of axonal defects and increased amyloid-beta peptide levels and amyloid deposition. Reductions in microtubule-dependent transport may stimulate proteolytic processing of beta-amyloid precursor protein, resulting in the development of senile plaques and Alzheimer's disease.

Aged↗

PubMed2005

Divalproex sodium in nursing home residents with possible or probable Alzheimer Disease complicated by agitation: a randomized, controlled trial.

OBJECTIVE: Three placebo-controlled clinical trials have suggested the benefit of valproate for treatment of agitation associated with dementia; one was used as the basis for this multicenter trial, conducted by the Alzheimer's Disease (AD) Cooperative Study. It addresses the efficacy, safety, and tolerability of divalproex sodium for the treatment of agitation associated with dementia. METHODS: This was a randomized, double-blind, placebo-controlled clinical trial in 153 nursing home residents with probable or possible AD complicated by agitation; 110 (72%) completed the trial. Participants were randomized to treatment with divalproex sodium at a target dose of 750 mg/day (N = 75) or placebo (N = 78) for 6 weeks. The primary outcome measure was change from baseline on the Brief Psychiatric Rating Scale (BPRS) Agitation factor. Secondary outcomes included total BPRS, Clinical Global Impression of Change, Cohen-Mansfield Agitation Inventory score, and measures of safety and tolerability. RESULTS: Compliance averaged 88%. Participants receiving divalproex achieved a mean dose of 800 mg/day. Change in mean BPRS Agitation factor scores did not differ between patients treated with divalproex and placebo, nor did secondary behavioral measures. Measures of safety and tolerability did not reveal clinically important drug/placebo differences. CONCLUSIONS: This multicenter trial showed no benefit of divalproex sodium for treatment for agitation in dementia at a mean dose of 800 mg/day over 6 weeks. The results do not support findings from previous trials indicating possible benefit.

Aged↗

PubMed2003

The Black Seventh-Day Adventist exploratory health study.

African Americans are at high risk for stroke and dementia. Modifications of lifestyle, however, might lower this risk. The Seventh-Day Adventist (SDA) Church encourages both spiritual adherence and a healthy lifestyle. Members are encouraged to exercise and are discouraged from smoking, drinking alcoholic or caffeinated beverages, or eating meat. The present study describes an exploratory project in 2 Black SDA congregations (N = 82) designed to characterize the lifestyle, dietary, and spiritual health habits of these congregations, and to test the feasibility of collecting such information in the Black SDA community at large. Three separate data collection methods are described and evaluated. Data demonstrate that the sample differs significantly from the African-American community at large in dietary, lifestyle, and spiritual health habits. The Black SDA community represents a unique opportunity to test the effects of diet, lifestyle, and spirituality on risk for stroke and dementia.

Black or African American↗

PubMed2003

Are there differences in risk factor profiles and frequency of CT/MRI-based infarcts among African American stroke patients with and without hypertension? A report from the African American Antiplatelet Stroke Prevention Study (AAASPS).

UNLABELLED: BACKGROUND; African Americans (AAs) have a high risk of stroke and a high prevalence of cardiovascular risk factors. Little is known about stroke risk profiles among non-hypertensive AAs. METHODS: African American Antiplatelet Stroke Prevention Study (AAASPS) enrollees with a history of hypertension (htn) were compared to those without htn for history of traditional cardiovascular risk factors and number and distribution of CT/MRI infarcts. Estimated odds ratios are presented describing the association between selected risk factors and htn status. The estimated odds ratios and 95% confidence intervals (CI) were obtained using multivariate logistic regression. RESULTS: The database for this analysis included 1012 patients with htn and 74 patients without htn. When compared to those with htn, those without htn were more commonly men (59% vs. 46%; p = 0.030), current cigarette smokers (55% vs. 37%; p = 0.001), were younger (median age: 59 years vs. 62 years; p = 0.064), had higher education (11.7 +/- 2.9 vs. 11.1 +/- 3.1; p = 0.024), had a higher number of acute strokes of unknown cause (23% vs. 13%; p=0.060), and less commonly had a history of diabetes (25% vs. 41%; p = 0.007). Those without htn had a lower mean number of old infarcts on MRI (0.94 +/- 1.40 vs. 1.45 +/- 1.60; p = 0.045), and a higher number of mean recent infarcts on CT (1.30 +/- 1.15 vs. 0.93 +/- 1.01; p = 0.031). Multivariate analysis to predict those without htn showed that these patients were more likely to be current cigarette smokers (OR = 2.89; CI = 1.60,5.49) and have higher education (OR = 1.08, CI = 0.996,1.17), and were less likely to have old CT/MRI-based infarcts (OR = 0.46; CI = 0.26,0.76). CONCLUSIONS: AAs without htn may have a different cardiovascular risk factor profile and CT/MRI profile than AAs with htn. This baseline profile among AAs without htn may predict lower stroke recurrence rates in this ongoing trial.

Black or African American↗

PubMed2002

Progressive worsening of spatial and chromatic processing deficits in Parkinson disease.

CONTEXT: Impairments of color discrimination (CD) and contrast sensitivity are established signs of Parkinson disease (PD), but their temporal evolution has not been studied. OBJECTIVE: To determine whether there is progressive, longitudinal deterioration of color discrimination (CD) and contrast sensitivity (CS) in PD. DESIGN: A prospective study. SETTING: Tertiary care center-based sample of PD patients without dementia with normal visual acuity (Snellen fraction >0.6 in the best eye). MAIN OUTCOME MEASURES: With a mean +/- SD interval of 19.8 +/- 2.8 months, the following tests were applied twice in 28 patients: the Lanthony D15 test and the Farnsworth Munsell 100 Hue test as tests of CD and the monocular and binocular Pelli-Robson test and the binocular Vistech tables as tests of CS. RESULTS: There was deterioration of both CD (Farnsworth Munsell 100 hue test: P =.002) and CS (binocular Vistech test at a spatial frequency of 6 cycles per degree, P<.001). Both deficits correlated with age, and the chromatic deficit additionally correlated with higher impairment of motor function (Unified Parkinson's Disease Rating Scale motor section, P =.04) and activities of daily life (Unified Parkinson's Disease Rating Scale activities of daily living section, P =.006). Patients with the highest pathologic psychiatric rating score (Brief Psychiatric Rating Scale) performed worse on both CS (P =.02) and CD (P =.01) at the second examination. CONCLUSIONS: Impairments of CD and CS in PD are progressive over time. Visual deficits may influence overall motor function and lead to enhanced motor impairment.

Aged↗

PubMed2002

Placebo-associated improvements in motor function: comparison of subjective and objective sections of the UPDRS in early Parkinson's disease.

The Unified Parkinson's Disease Rating Scale (UPDRS) is primarily composed of an investigator-derived objective rating of motor function and a patient-derived assessment of activities of daily living (ADL). Using a stringent definition of placebo effect, we examined the frequency, temporal development, and stability of improvements during placebo treatment over 6 months in a large placebo-controlled trial of deprenyl and tocopherol in early Parkinson's disease (DATATOP). One hundred ninety-nine subjects received placebo treatment in the randomized, multicenter, placebo-controlled DATATOP study. We compared the baseline UPDRS motor section scores with follow-up scores at 4, 13, and 26 weeks. Placebo-associated improvement was defined as an improvement over baseline score in motor UPDRS of at least 50% or a change in at least two motor items at any one visit by two or more points. Seventeen percent of the 185 subjects who qualified for analysis met the placebo response criteria. The group prevalence of response was steady (7% to 10%) at any one visit without a marked predominance of an early study effect. Older subjects with more motor impairment at baseline were most likely to show a placebo-associated improvement. ADL scores were low throughout the study, and ADL improvements did not identify the subjects with objectively defined placebo-associated improvement. Prominent improvements in investigator-derived objective measures of Parkinson's disease motor impairment occur during clinical trials, including one that was not aimed at showing improved short-term efficacy. Although the notion of placebo effect often implies patient-based perceptions, we found subjective changes to be infrequent in placebo-treated patients, suggesting that either: (1) the placebo effect was rater-driven; (2) the ADL questionnaire is insensitive to transient but objectively demonstrable motor changes; or (3) that the objective changes, albeit major, are within the realm of natural variation in the UPDRS motor scale from visit to visit.

Activities of Daily Living↗

PubMedDate not supplied

Dopaminergic hypersensitivity in patients with Parkinson disease and migraine.

Because migraine has been associated with dopaminergic receptor hypersensitivity, the authors hypothesized that patients with Parkinson disease with current or prior migraine have better dopaminergic response and less motor disability than Parkinson disease patients without migraine. Twenty-eight patients with Parkinson disease were included and matched (10 patients with migraine and 18 patients without migraine). Patients with Parkinson disease and migraine showed greater motor improvement during the ON state than patients without migraine with the same medication exposure. These data support the hypothesis that migraine may be associated with dopaminergic hypersensitivity.

Aged↗

PubMedDate not supplied

ADCS Prevention Instrument Project: behavioral measures in primary prevention trials.

BACKGROUND: There is an urgent need for the development of inexpensive, reliable, and valid instruments that can be used in large-scale primary prevention trials of compounds aimed at ameliorating progression from normal aging to mild cognitive impairment or Alzheimer disease. The Alzheimer's Disease Cooperative Study launched a Prevention Instrument Project to develop such methodologies. Behavioral changes are common in diseases causing dementia and may occur prior to a point when cognitive changes are sufficiently severe to allow diagnosis of a dementia syndrome. Experimental behavioral measures were included in the protocol to examine this hypothesis. METHODS: Six hundred forty-four individuals with CDR 0 or 0.5 were randomly assigned to receive a brief in-clinic behavioral assessment or telephonic administration of the same assessment. The questions were asked to the individual and their research partner. The Prevention Instrument Project included behavioral measures of depression, anxiety, irritability, and apathy. RESULTS: All measures demonstrated acceptable test-retest reliability at 3-month intervals except for the single-item depression screen by the subjects' research partner. Behavioral changes are significantly more common among patients with Clinical Dementia Rating (CDR) scores of 0.5 compared with CDR scores of 0. Behavioral alterations including irritability, anxiety, and apathy are more common among ethnic minorities than among the White population. Depression, irritability, anxiety, and apathy are significantly correlated with each other. CONCLUSIONS: Behavioral changes are common among those with mild degrees of cognitive compromise (CDR 0.5). Telephonic assessment of behavioral changes is feasible. The predictive value of these alterations for progression to Alzheimer disease or other dementias will be assessed longitudinally.

Activities of Daily Living↗

PubMedDate not supplied

ADCS Prevention Instrument Project: ADCS-clinicians' global impression of change scales (ADCS-CGIC), self-rated and study partner-rated versions.

BACKGROUND: Because primary prevention trials will require large samples and modest treatment effects are expected, the use of standard clinician-administered, clinic-based measures are unlikely to be feasible. There is a need for proxy-administered outcome measures. The goal of the Alzheimer's Disease Cooperative Study (ADCS) Prevention Instrument Project was to conduct a simulated Alzheimer disease prevention trial in 650 nondemented elderly (Ferris et al, 2006). This involved comparison of data acquisition from both home and clinic and the use of both informant-ratings and self-ratings. Important outcomes included clinical global impressions of change (CGIC) as indicators of clinically meaningful change. Such ratings provide verification that the effects of a medication as measured on rating scales are readily observable and clinically meaningful. One objective was to develop self-rated and study partner-rated CGICs optimized for nondemented elderly or people with very early Alzheimer disease. An important consideration was whether global assessments are specific and sensitive measures of change during a prevention trial. METHODS: A self-administered CGIC and a study partner-rated CGIC were developed to be used either in the clinic or at home. Using 3-month follow-up data, we determined its reliability and validity with 317 subject-partner pairs. We compared subject-ratings with partner-ratings, clinic-based with home-based ratings, and ratings based on severity as determined by the Clinical Dementia Rating scale. RESULTS: There were no differences between clinic and home ratings. Overall, 24% of subjects rated themselves, and 10% of study partners rated the subjects, as minimally to markedly improved. Subjects and partners agreed to within 1 point of their ratings 83% of the time on the 7-point scale. There were weak correlations, generally <0.20, with change scores of selected clinical rating scales. DISCUSSION: The CGICs behaved as expected, showing no overall change over 3 months, no difference between administrations at home compared with clinics, and concurrent validity. Some subjects tended to rate themselves better than their partners rated them. These analyses show the potential for using home-based CGICs which can be completed with minimal supervision and allow assessments of potential preventative interventions.

Activities of Daily Living↗

PubMedDate not supplied

ADCS Prevention Instrument Project: the Mail-In Cognitive Function Screening Instrument (MCFSI).

In future research on the prevention of Alzheimer Disease (AD), a large simple prevention trial might test a safe intervention (eg, vitamins) in a very large population (eg, 10,000 subjects), powered to detect a modest treatment effect size. In a large, simple design, regular assessments must be very low cost, for example, handled by mail. The Mail-In Cognitive Function Screening Instrument (MCFSI) was developed for the Alzheimer's Disease Cooperative Study Prevention Instrument Project to evaluate whether a brief mail-in screening tool can be used as a specific and sensitive trigger for a diagnostic evaluation in the course of a prevention trial. The MCFSI consists of 2 similar sets of 14 questions mailed separately to the subject and the study partner, who are asked to complete them independently. The questions are derived from a standard clinical assessment of dementia; they ask about decline in function over the last year. We are currently evaluating the utility of the instrument in 640 subjects over the course of the "simulated" AD prevention trial. Analysis of baseline data showed significant differences in mean MCFSI scores between sex and ethnic groups (for subjects), age groups (for partners), and Clinical Dementia Rating global score groups (both subject and partner). In this nondemented population, both subject's and partner's MCFSI responses were related to cognitive performance. There was no significant association between MCFSI score for either subjects or partners and apolipoprotein E genotype. The MCFSI captures information related to cognitive and functional status in nondemented elderly individuals; the Alzheimer's Disease Cooperative Study Prevention Instrument Project will determine whether this brief, mail-in questionnaire is useful as a trigger for diagnostic evaluation in an AD primary prevention trial.

Activities of Daily Living↗