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Russell Steele

Publications and source records attributed to Russell Steele.

9 recordsLinked to original sources

Development of the McGill Range of Motion Index.

We created the McGill Range of Motion Index (McROMI) to allow us to ascribe a score to global limited range of motion (ROM) in patients with polyarthritis. Our goal was to have an easy-to-use index that required only visual estimation of ROM and could be performed by allied health professionals with limited training. The index was created with a range of motion ranking technique involving rheumatologists at McGill University and its validity was tested in patients with early inflammatory arthritis in the McGill Early Arthritis Registry. We hypothesized a valid index would correlate with various process and outcome measures. We found correlations between the McROMI and function (Health Assessment Questionnaire), Health Related Quality of Life (SF-36), pain, a global assessment of inflammatory disease activity (DAS28), and the number of tender and swollen joints. The McROMI demonstrates good validity as a measure of ROM in early inflammatory arthritis. It will prove useful in future research as a means of controlling for ROM as a confounder of various outcomes and in studies of therapeutic maneuvers to improve ROM.

Arthritis↗

Selecting immunohistochemical cut-off scores for novel biomarkers of progression and survival in colorectal cancer.

BACKGROUND: Cut-off scores for determining positivity of biomarkers detected by immunohistochemistry are often set arbitrarily and vary between reports. AIMS: To evaluate the performance of receiver operating characteristic (ROC) curve analysis in determining clinically important cut-off scores for a novel tumour marker, the receptor for hyaluronic acid mediated motility (RHAMM), and show the reproducibility of the selected cut-off scores in 1197 mismatch-repair (MMR) proficient colorectal cancers (CRC). METHODS: Immunohistochemistry for RHAMM was performed using a tissue microarray of 1197 MMR-proficient CRC. Immunoreactivity was scored using a semi-quantitative scoring method by evaluating the percentage of positive tumour cells. ROC curve analysis was performed for T stage, N stage, tumour grade, vascular invasion and survival. The score with the shortest distance from the curve to the point with both maximum sensitivity and specificity, i.e. the point (0.0, 1.0), was selected as the cut-off score leading to the greatest number of tumours correctly classified as having or not having the clinical outcome. In order to determine the reliability of the selected cut-off scores, 100 bootstrapped replications were performed to resample the data. RESULTS: The cut-off score for T stage, N stage, tumour grade and vascular invasion was 100% and that for survival 90%. The most frequently selected cut-off score from the 100 resamples was also 100% for T stage, N stage, tumour grade, and vascular invasion and 90% for survival. CONCLUSIONS: ROC curve analysis can be used as an alternative method in the selection and validation of cut-off scores for determining the clinically relevant threshold for immunohistochemical tumour positivity.

Biomarkers, Tumor↗

Office capillaroscopy in systemic sclerosis.

The aims of this study are to assess the reliability of two office techniques, the ophthalmoscope and the Dermlite dermatoscope, and to detect nailfold capillaroscopy abnormalities in systemic sclerosis (SSc). Two separate studies were performed. In the first, the nailfolds of two fingers on one hand of 13 SSc patients and two normals were examined by four rheumatologists using an ophthalmoscope. In the second, the nailfolds of the two fingers of each hand of six SSc patients and two normals were examined by six rheumatologists with a Dermlite dermatoscope. Widefield capillary microscopy was performed by one observer in the ophthalmoscope study to assess validity. The examiners determined the presence or absence of dilated loops, giant capillary loops, and/or avascular areas on each digit. The kappa coefficient was calculated to demonstrate agreement. With the ophtalmoscope, the inter-observer kappa coefficients were 0.43, 0.54, and 0.19; the average intra-observer agreements were 0.61, 0.56, and 0.31; and the ophthalmoscope-microscope agreement were 0.63, 0.52, and <0.1 for dilated capillaries, giant capillaries, and avascular areas, respectively. With the dermatoscope, the kappa values for inter-observer reliability were 0.63, 0.40, and 0.20; and intra-observer reliability was 0.71, 0.55, and 0.40 for dilated capillaries, giant capillaries, and avascular areas, respectively. The ophthalmoscope and the dermatoscope provide moderate to substantial reliability to detect the presence of giant and dilated capillaries but poor inter-observer agreement for avascular areas. The ophthalmoscope is valid when compared to the microscope for detecting giant or dilated capillaries. We conclude that these techniques are useful office tools to detect capillary abnormalities in SSc.

Dermoscopy↗

Scoring of p53, VEGF, Bcl-2 and APAF-1 immunohistochemistry and interobserver reliability in colorectal cancer.

Molecular tumor markers are often studied in colorectal cancer using immunohistochemistry to determine their prognostic or predictive value. Protein expression is typically assigned a 'positive' score based on a predetermined cutoff. A semiquantitative scoring method that evaluates the percentage of positive tumor cells (0-100%) may provide a better understanding of the prognostic or predictive significance of these markers. The aim of this study was to assess and compare the interobserver agreement of immunohistochemistry scores using a percentage scoring method and three categorical scoring systems. Immunohistochemistry for p53, Bcl-2, vascular endothelial growth factor (VEGF) and apoptotic protease activating factor-1 (APAF-1) was performed on 87 tumor biopsies from patients with rectal carcinoma and scored independently by four pathologists as the percentage of positive tumor cells. Interobserver agreement was assessed by the intraclass correlation coefficient. The intraclass correlation coefficients for p53 and VEGF (>0.6) indicate substantial agreement between observers. The distribution of Bcl-2 and APAF-1 scores in addition to weaker interobserver agreement by percentage scoring suggest that this approach may not be appropriate for these proteins. In conclusion, p53 and VEGF protein expression assessed by immunohistochemistry in colorectal cancer and scored as a percentage of positive tumor cells may be a viable alternative scoring method.

Adenocarcinoma↗

Understanding the relationship between risks and odds ratios.

BACKGROUND: Many articles provide only odds ratios (OR) and non relative risks (RR) as the effect estimate. For a variety of important reasons, multiple logistic regression used to adjust for confounders routinely provides only the adjusted OR (ORadj). However, from the clinician's perspective, the ORadj is only easily interpretable when it approximates the adjusted RR (RRadj). In general, the relationship between the OR and RR (adjusted or nonadjusted) is dependent on prevalence of disease in the control group (Po) and has always been presented as nonlinear. Therefore, it is difficult for the clinician to convert the OR to RR when reading the published data. A formula was proposed by Zhang and Yu, but the relationship remains nonlinear. OBJECTIVE: To develop a simple method to convert OR to RR without the use of computer. METHODS: Algebraic manipulation. RESULTS: Through algebraic manipulation, we show that although the OR and RR relationship is nonlinear over the range Po, the ratio OR/RR has a linear relationship with Po with a slope of "OR-1": OR/RR=(OR-1)xPo+1. This makes the prediction of RR on the basis of OR more transparent. It is clear that if Po is small, the RR approximates the OR, but only if the OR is also small. Previous problems with confidence intervals noted with the Zhang and Yu formula remain (ie, they are too narrow under some conditions) and the result should be interpreted with this limitation. Relationships between ORadj and risk difference or number needed to treat remain curvilinear, but some overall approximations can be made. CONCLUSION: A simple relationship exists that allows readers to easily convert ORadj to RRadj. Limitations of the approach remain but seem to be less restrictive than the limitations of not converting ORadj to RRadj.

Mathematics↗

VEGF as a predictive marker of rectal tumor response to preoperative radiotherapy.

BACKGROUND: Neoadjuvant radiotherapy for rectal cancer may result in tumor downstaging or complete tumor regression leading to greater sphincter preservation. The identification of molecular predictive markers of tumor response to preoperative radiotherapy would provide an additional tool for selecting patients most likely to benefit from treatment. The aim of this study was to determine whether VEGF expression in preirradiation tumor biopsies is a useful predictive marker of tumor response in patients with rectal cancer undergoing preoperative radiotherapy. METHODS: Immunohistochemistry for VEGF was performed on 59 preirradiation biopsies from patients with completely responsive (ypT0) or nonresponsive tumors after preoperative radiotherapy. VEGF positivity was evaluated using several scoring methods and the association between VEGF and tumor response was compared. The distribution of VEGF scores was obtained as well as the mean VEGF expression in the two response groups. RESULTS: The mean VEGF expression in nonresponsive tumors (NR) was significantly greater than in completely responsive tumors (CR) (P = 0.0035). Nearly half (47%) of all CR tumors had a VEGF expression of 10% or less. Eleven tumors were negative (0% immunoreactivity) for the protein and all of these (100%) were complete responders. Fifty-two percent of the NR tumors had VEGF scores of 80% or greater. The four scoring methods used to determine the association between VEGF and tumor response each produced significant results (P < 0.05). CONCLUSIONS: The results of this study indicate that VEGF assessed immunohistochemically from preirradiation tumor biopsies may be a useful marker of rectal tumor response to preoperative radiotherapy.

Adenocarcinoma↗

A predictive model of rectal tumor response to preoperative radiotherapy using classification and regression tree methods.

PURPOSE: The ability to predict rectal tumor response to preoperative radiotherapy before treatment would significantly impact patient selection. In this study, classification and regression tree (CART) methods were used to model tumor response to preoperative conformal high-dose rate brachytherapy by assessing the predictive value of vascular endothelial growth factor (VEGF), Bcl-2, p21, p53, and APAF-1. EXPERIMENTAL DESIGN: Immunohistochemistry was used to detect VEGF, Bcl-2, p21, p53, and APAF-1 from 62 pretreatment rectal tumor biopsies. Scores were assigned as percentages of positive tumor cell staining and were used in CART analysis to identify the proteins that best predicted response to radiotherapy. Ten-fold cross-validation was used to prevent overfitting and multiple cross-validation experiments were run to estimate the prediction error. RESULTS: Postoperative pathologic evaluation of the irradiated tumor bed revealed 43 responsive tumors [20 with complete response (T(0)) and 23 with partial response] and 19 nonresponsive tumors. The optimal tree resulting from CART analysis had five terminal nodes with a misclassification rate of 18%. Of the five proteins selected for their predictive value, VEGF and Bcl-2 contributed most to the classification of responsive and nonresponsive tumors. All 10 tumors with no VEGF were completely responsive (T(0)) to radiotherapy; 85% of those with VEGF and negative for Bcl-2 were responsive to therapy. CONCLUSIONS: VEGF and Bcl-2 status in pretreatment rectal tumor biopsies may be predictive of response to preoperative high-dose rate brachytherapy.

Apoptotic Protease-Activating Factor 1↗

Formulations of antibiotics for children in primary care: effects on compliance and efficacy.

This review article is designed for pediatricians as well as primary care physicians in the outpatient setting as a clinical guide to antibiotic selection. It emphasizes variables related to compliance as well as efficacy. The aim is to give recommendations as to the choice of antibiotics, depending on factors such as taste, cost, efficacy, and compliance. Common bacterial pathogens causing infections in children are reviewed, along with their susceptibility patterns to antimicrobial agents. Emerging mechanisms of resistance, particularly the increasing resistance of pneumococci to beta-lactam antibiotics, are discussed because of their importance to antibiotic selection. Previously published studies that have examined the treatment of common outpatient infections in children, such as otitis media, streptococcal tonsillopharyngitis, and sinusitis, are summarized. Adverse reactions associated with antibiotics, second in importance only to efficacy, are reviewed. Finally, compliance issues, which include palatability, cost, duration of therapy, and administration frequency, are analyzed using recently published information related to each of these issues. The efficacy of the commonly used antibiotics for urinary tract infections, pneumonia, and streptococcal pharyngitis does not vary significantly; however, for otitis media and sinusitis, some studies have shown that treatment efficacy with the antibiotic does not vary significantly from that with placebo. Likewise, adverse reactions rarely provide a basis for antibiotic selection, since virtually all antibiotics are generally well tolerated. The final factor, compliance, is a major issue in determining both first- and second-line therapy of common outpatient infections in children. Although cost is not a factor in compliance in countries such as the UK where no copayment is required for pediatric drugs, it is of major importance in the US. This is followed by palatability, administration duration and finally administration frequency. As a group, cephalosporins are generally the best tasting but are relatively more expensive than macrolides. Antibiotics that can be given for 5 days, and just once or twice daily, are preferred by most parents and physicians. Since final assessment of antibiotic choice is likely to vary considerably among healthcare personnel, decisions must be made on an individual basis.

Anti-Bacterial Agents↗