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Scott Hamilton

Publications and source records attributed to Scott Hamilton.

10 recordsLinked to original sources
PubMed2006

Magnetic resonance imaging profiles predict clinical response to early reperfusion: the diffusion and perfusion imaging evaluation for understanding stroke evolution (DEFUSE) study.

OBJECTIVE: To determine whether prespecified baseline magnetic resonance imaging (MRI) profiles can identify stroke patients who have a robust clinical response after early reperfusion when treated 3 to 6 hours after symptom onset. METHODS: We conducted a prospective, multicenter study of 74 consecutive stroke patients admitted to academic stroke centers in North America and Europe. An MRI scan was obtained immediately before and 3 to 6 hours after treatment with intravenous tissue plasminogen activator 3 to 6 hours after symptom onset. Baseline MRI profiles were used to categorize patients into subgroups, and clinical responses were compared based on whether early reperfusion was achieved. RESULTS: Early reperfusion was associated with significantly increased odds of achieving a favorable clinical response in patients with a perfusion/diffusion mismatch (odds ratio, 5.4; p = 0.039) and an even more favorable response in patients with the Target Mismatch profile (odds ratio, 8.7; p = 0.011). Patients with the No Mismatch profile did not appear to benefit from early reperfusion. Early reperfusion was associated with fatal intracranial hemorrhage in patients with the Malignant profile. INTERPRETATION: For stroke patients treated 3 to 6 hours after onset, baseline MRI findings can identify subgroups that are likely to benefit from reperfusion therapies and can potentially identify subgroups that are unlikely to benefit or may be harmed.

Aged↗
PubMed2005

Transmissible spongiform encephalopathy strain, PrP genotype and brain region all affect the degree of glycosylation of PrPSc.

Transmissible spongiform encephalopathies (TSEs), sometimes known as prion diseases, are caused by an infectious agent whose molecular properties have not been determined. Traditionally, different strains of TSE diseases are characterized by a series of phenotypic properties after passage in experimental animals. More recently it has been recognized that diversity in the degree to which an abnormal form of the host protein PrP, denoted PrP(Sc), is glycosylated and the migration of aglycosyl forms of PrP(Sc) on immunoblots may have some differential diagnostic potential. It has been recognized that these factors are affected by the strain of TSE agent but also by other factors, e.g. location within the brain. This study shows in some cases, but not others, that host PrP genotype has a major influence on the degree of PrP(Sc) glycosylation and migration on gels and provides further evidence of the effect of brain location. Accordingly both the degree of glycosylation and the apparent molecular mass of PrP(Sc) may be of some value for differential diagnosis between TSE strains, but only when host effects are taken into account. Furthermore, the data inform the debate about how these differences arise, and favour hypotheses proposing that TSE agents affect glycosylation of PrP during its biosynthesis.

Animals↗
PubMed2004

Beyond subgroup analysis: improving the clinical interpretation of treatment effects in stroke research.

In large clinical trials designed to determine efficacy of an experimental treatment, patients are enrolled with presence or absence of various risk factors, such as diabetes or history of atrial fibrillation. A treatment-by-risk factor interaction indicates that the treatment effect may depend on the risk factor presence or absence. It is important to identify such interaction, since a treatment may fail or cause adverse events in the presence of the risk. Although statistical methods exist to identify such interaction, they are underutilized in clinical stroke research. This paper reviews the notion of treatment-by-risk factor interaction and identifies two types of interaction, quantitative and qualitative, using a graphical technique and statistical testing. We illustrate how to avoid drawing the erroneous conclusions regarding the treatment effect on subgroups when failing to detect an interaction, and provide rigorous tools to estimate the treatment effect on subgroups when an interaction is observed. Applications are presented using the data collected from the NINDS t-PA stroke studies. In stroke clinical trials, a treatment-by-risk factor interaction must be considered if the data permit. The graphical approach provides a heuristic illustration of interactions. Qualitative interactions are more important than quantitative interactions on therapeutic conclusion. Results of NINDS t-PA stroke studies confirmed our previous conclusions on the treatment t-PA benefit within 3-h therapeutic window. No subgroup of patients would lead a physician to withhold the t-PA treatment.

Algorithms↗
PubMed2004

Association of outcome with early stroke treatment: pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke trials.

BACKGROUND: Quick administration of intravenous recombinant tissue plasminogen activator (rt-PA) after stroke improved outcomes in previous trials. We aimed to analyse combined data for individual patients to confirm the importance of rapid treatment. METHODS: We pooled common data elements from six randomised placebo-controlled trials of intravenous rt-PA. Using multivariable logistic regression we assessed the relation of the interval from stroke onset to start of treatment (OTT) on favourable 3-month outcome and on the occurrence of clinically relevant parenchymal haemorrhage. FINDINGS: Treatment was started within 360 min of onset of stroke in 2775 patients randomly allocated to rt-PA or placebo. Median age was 68 years, median baseline National Institute of Health Stroke Scale (NIHSS) 11, and median OTT 243 min. Odds of a favourable 3-month outcome increased as OTT decreased (p=0.005). Odds were 2.8 (95% CI 1.8-4.5) for 0-90 min, 1.6 (1.1-2.2) for 91-180 min, 1.4 (1.1-1.9) for 181-270 min, and 1.2 (0.9-1.5) for 271-360 min in favour of the rt-PA group. The hazard ratio for death adjusted for baseline NIHSS was not different from 1.0 for the 0-90, 91-180, and 181-270 min intervals; for 271-360 min it was 1.45 (1.02-2.07). Haemorrhage was seen in 82 (5.9%) rt-PA patients and 15 (1.1%) controls (p<0.0001). Haemorrhage was not associated with OTT but was with rt-PA treatment (p=0.0001) and age (p=0.0002). INTERPRETATION: The sooner that rt-PA is given to stroke patients, the greater the benefit, especially if started within 90 min. Our results suggest a potential benefit beyond 3 h, but this potential might come with some risks.

Aged↗
PubMed2004

Granulocyte-macrophage colony-stimulating factor gene-modified autologous tumor vaccines in non-small-cell lung cancer.

To evaluate the feasibility, safety, and efficacy of vaccination with autologous tumor cells genetically modified with an adenoviral vector (Ad-GM) to secrete human granulocyte-macrophage colony-stimulating factor (GM-CSF), we conducted a phase I/II multicenter trial in patients with early and advanced stage non-small-cell lung cancer (NSCLC). Vaccines were generated from autologous tumor harvests. Intradermal injections were given every 2 weeks for a total of three to six vaccinations. Tumors were harvested from 83 patients, 20 with early-stage NSCLC and 63 with advanced- stage NSCLC; vaccines were successfully manufactured for 67 patients, and 43 patients were vaccinated. The most common toxicity was a local injection-site reaction (93%). Three of 33 advanced-stage patients, two with bronchioloalveolar carcinoma, had durable complete tumor responses (lasting 6, 18, and >or=22 months). Longer survival was observed in patients receiving vaccines secreting GM-CSF at more than 40 ng/24 h per 10(6) cells (median survival = 17 months, 95% confidence interval [CI] = 6 to 23 months) than in patients receiving vaccines secreting less GM-CSF (median survival = 7 months, 95% CI = 4 to 10 months) (P =.028), suggesting a vaccine dose-related survival advantage.

Adult↗
PubMed2004

Computed tomographic volumetric analysis as a predictor of local control in laryngeal cancers treated with conventional radiotherapy.

BACKGROUND: There is still controversy regarding the appropriate management of large T2 and T3 laryngeal cancers, with some investigators finding little correlation between the current TNM staging system and tumour control following external beam radiotherapy. OBJECTIVE: To establish the utility of computed tomography (CT)-determined tumour volume as a predictor of local control of moderately advanced (T2 and T3) squamous cell carcinoma of the larynx. MATERIALS AND METHODS: A retrospective chart review and CT volumetric analysis were performed on 47 patients who were treated for T2 or T3 laryngeal squamous cell carcinoma with radiotherapy alone at the London Regional Cancer Centre between 1995 and 2000. Of these 47 patients, there were 30 with glottic tumours and 17 with supraglottic tumours. Forty-two males and five females were included in the analysis, with ages ranging from 40 to 84 years. Each patient's CT scan was redigitized, and the tumours were outlined by the chief investigator and by a head and neck radiologist using anatomy modelling software. Patient demographics, tumour characteristics, and tumour stage were analyzed, with local failure rates described and related to the variables through univariate and multivariate analyses. RESULTS: Tumour size ranged from 0.15 to 16.64 cm3, with a mean volume of 3.5 cm3. The local recurrence rate in this group of patients was 40% (19/47). Local control was correlated on multivariate analysis to tumour size for all patients combined (> 3 cm3 vs < 3 cm3; p = .003) and for glottic tumours alone (> 1 cm3 vs < 1 cm3; p = .001). A correlation was also demonstrated on multivariate analysis between local control and overall stage (p = .023), patient age (p = .029), and hypopharyngeal involvement (p = .032). CONCLUSIONS: There is a significant and independent relationship between CT-determined tumour volume and local recurrence in moderately advanced squamous cell carcinoma of the larynx treated with conventional radiotherapy. Based on these results and those of similar studies, CT should therefore become a routine part of the staging system for T2 tumours and above.

Adult↗
PubMed2002

Shortening the NIH Stroke scale for use in the prehospital setting.

BACKGROUND AND PURPOSE: Prehospital stroke scales should identify stroke patients and measure stroke severity. The goal of this study was to identify a subset of the 15 items in the National Institutes of Health Stroke Scale (NIHSS-15) that measures stroke severity and predicts outcomes. METHODS: Using 2 distinct data sets from acute stroke clinical trials, we derived and validated shortened versions of the NIHSS (sNIHSS). Stepwise logistic regression and bootstrap techniques were used in selection of NIHSS-15 items. Areas under the receiver operator characteristic curve (C statistics) were used to compare predictive performance of logistic models incorporating differing versions of the NIHSS. RESULTS: The derivation analyses suggested the 8 NIHSS-15 items that were most predictive of "good outcome" 3 months after stroke, in order of decreasing importance: right leg item, left leg, gaze, visual fields, language, level of consciousness, facial palsy, and dysarthria. The sNIHSS-8 comprises all 8 and the sNIHSS-5, the first 5. In the validation models, C statistics were NIHSS-15=0.80, sNIHSS-8=0.77, and sNIHSS-5=0.76. Statistical comparisons suggested that the NIHSS-15 had better predictive performance than the sNIHSS-8 or the sNIHSS-5; the absolute difference in C statistics was small. There was no significant difference between the sNIHSS-8 and the sNIHSS-5. CONCLUSIONS: Much of the predictive performance of the full NIHSS-15 was retained with a shortened scale, the sNIHSS-5. Shortening the NIHSS-15 will facilitate its use during prehospital evaluations. The sNIHSS severity information may be useful to triage acute stroke patients in communities and to provide a baseline stroke severity for prehospital acute stroke trials.

Acute Disease↗
PubMedDate not supplied

Novel cyanine dye-labeled dideoxynucleoside triphosphates for DNA sequencing.

Single color cyanine dye-labeled (Cy 5.0 and Cy 5.5) dideoxynucleoside-5'-triphosphates, or 'terminators', containing different spacer lengths were synthesized and evaluated for efficacy in DNA sequencing methods using a modified thermally stable DNA polymerase. The single color cyanine dye terminators were formulated into two separate sets of sequencing mixes, one for Cy 5.0 and the other for Cy 5.5, and evaluated on different automated sequencing platforms. Each set of mixes included two pyrimidine terminators with 17-atom linkers and two purine terminators with 10-atom linkers between the dye and the nucleotide. The two sets of cyanine dye-labeled terminators chosen for this cycle sequencing study produced improved band patterns with band uniformity similar to that obtained with dye-primer sequencing methods.

Base Sequence↗