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Correlation of transrectal ultrasound imaging and the results of systematic biopsy with pathological examination of radical prostatectomy specimens.

OBJECTIVE: To determine the usefulness of transrectal ultrasound (TRUS) and systematic biopsy by correlating these results with pathological findings after radical prostatectomy. PATIENTS AND METHODS: Pre-operative TRUS examination combined with the findings on systematic biopsy in 15 patients (mean age 70.6 years, range 57-87) who underwent radical prostatectomy between October 1992 and February 1994 were compared retrospectively to the histological features of whole mount sections of the surgical specimens. RESULTS: In all cases, the tumour was visualized as a hypoechoic area on the sonogram. In addition, in six of 15 cases the tumour was localized in an isoechoic area which was examined before the operation by systematic biopsy. In this series, a systematic biopsy before operating detected tumour grade and localization of the tumour in 14 and 15 patients, respectively. The positive predictive value of capsular penetration and seminal vesicle invasion on the sonogram was 0.71 and 1.00, respectively, while sensitivity was 1.00 and 0.33, respectively. Five of seven patients with findings of capsular penetration on the sonogram revealed capsular penetration in the resected prostate, whereas, of three patients with pathologically detected seminal vesical invasion, only one had findings of seminal vesicle invasion by ultrasonography. The serum prostate specific antigen level of all three patients was more than 30 ng/mL. Moreover, in this series of 15 patients TRUS detected the precise stage in 11 patients. In the remaining four patients, two were overstaged and two were understaged. Tumours with hypoechogenicity were of higher grade and larger than tumours with isoechogenicity. All tumours with hypoechogenicity were palpable and all with isoechogenicity were not. CONCLUSIONS: TRUS combined with a systematic biopsy was useful in predicting tumour grade, exact location and capsular penetration. However, it was not useful for determining tumour stage or predicting seminal vesicle invasion of prostate cancer. TRUS-guided seminal vesicle biopsy must be performed in patients with a serum prostate specific antigen of more than 30 ng/mL.

Adenocarcinoma↗

Designing systematic conservation assessments that promote effective implementation: best practice from South Africa.

Systematic conservation assessment and conservation planning are two distinct fields of conservation science often confused as one and the same. Systematic conservation assessment is the technical, often computer-based, identification of priority areas for conservation. Conservation planning is composed of a systematic conservation assessment coupled with processes for development of an implementation strategy and stakeholder collaboration. The peer-reviewed conservation biology literature abounds with studies analyzing the performance of assessments (e.g., area-selection techniques). This information alone, however can never deliver effective conservation action; it informs conservation planning. Examples of how to translate systematic assessment outputs into knowledge and then use them for "doing" conservation are rare. South Africa has received generous international and domestic funding for regional conservation planning since the mid-1990s. We reviewed eight South African conservation planning processes and identified key ingredients of best practice for undertaking systematic conservation assessments in a way that facilitates implementing conservation action. These key ingredients include the design of conservation planning processes, skills for conservation assessment teams, collaboration with stakeholders, and interpretation and mainstreaming of products (e.g., maps) for stakeholders. Social learning institutions are critical to the successful operationalization of assessments within broader conservation planning processes and should include not only conservation planners but also diverse interest groups, including rural landowners, politicians, and government employees.

Conservation of Natural Resources↗

Method of identifying dynamic multileaf collimator irradiation that is highly sensitive to a systematic MLC calibration error.

In intensity modulated radiotherapy (IMRT), radiation is delivered in a multiple of multileaf collimator (MLC) subfields. A subfield with a small leaf-to-leaf opening is highly sensitive to a leaf-positional error. We introduce a method of identifying and rejecting IMRT plans that are highly sensitive to a systematic MLC gap error (sensitivity to possible random leaf-positional errors is not addressed here). There are two sources of a systematic MLC gap error: centerline mechanical offset (CMO) and, in the case of a rounded end MLC, radiation field offset (RFO). In IMRT planning system, using an incorrect value of RFO introduces a systematic error ARFO that results in all leaf-to-leaf gaps that are either too large or too small by (2*DeltaRFO), whereas assuming that CMO is zero introduces systematic error DeltaCMO that results in all gaps that are too large by DeltaCMO=CMO. We introduce a concept of the average leaf pair Opening (ALPO) that can be calculated from a dynamic MLC delivery file. We derive an analytic formula for a fractional average fluence error resulting from a systematic gap error of Deltax and show that it is inversely proportional to ALPO; explicitly it is equal to Deltax/(ALPO+ 2 * RFO+ epsilon), in which epsilon is generally of the order of 1 mm and Deltax =2 * Delta RFO + CMO. This analytic relationship is verified with independent numerical calculations.

Algorithms↗

The elements of tissue-air ratio and systematic error.

The definition of tissue-air ratio (TAR) is based on the concept of primary dose. To determine TAR, both in-phantom and in-air ionization measurements are utilized. To convert ionization in the phantom into dose and that in air into primary dose, correction factors must be applied to chamber readings in both geometries. Due to difficulties in selecting proper correction factors, TAR is subject to systematic error. The error comes from two sources of uncertainty: (1) Primary dose cannot be measured. Therefore approximate methods, such as in-air ionization measurements, are used. (2) Detectors of ionization are of finite dimensions and they are inhomogeneous. In this study, analytical expression for a systematic error is derived. Because in this derivation systematic error is an accumulative error, it is no longer necessary to convert ionization, both in air and in phantom, into a dose when calculating TARs. A method of determining systematic error is described. This method is based on the ability to produce accurate zero-field data in photon beams by means of a linear extrapolation technique. Using 60Co gamma radiation in water as an example, it is shown how to generate TAR data free of systematic error. A possibility of determining TARs for therapeutic x rays is discussed.

Air Ionization↗

Reporting, updating, and correcting systematic reviews of the effects of health care.

The recent growth in the numbers of published systematic reviews reflects growing recognition of their importance for improving knowledge about the effects of health care. In Britain the NHS R&D Programme has established two centres to prepare systematic reviews of existing information, and the Cochrane Collaboration--an international network of individuals and institutions--evolved to produce systematic, periodically updated reviews of randomised controlled trials. The large amount of existing evidence that needs to be considered creates a problem for the reporting of systematic reviews: the need to ensure that methods and results of systematic reviews are adequately described has to be reconciled with the limited space available in printed journals. A possible solution is the use of electronic publications: reviews could be published simultaneously in a short, printed form and in a more detailed electronic form. Electronic publications also have the advantage of the ease with which reviews may be updated as new evidence becomes available or mistakes are identified.

Health Services Research↗

Optimal search strategies for retrieving systematic reviews from Medline: analytical survey.

OBJECTIVE: To develop optimal search strategies in Medline for retrieving systematic reviews. DESIGN: Analytical survey. DATA SOURCES: 161 journals published in 2000 indexed in Medline. MAIN OUTCOME MEASURES: The sensitivity, specificity, and precision of retrieval of systematic reviews of 4862 unique terms in 782,485 combinations of one to five terms were determined by comparison with a hand search of all articles (the criterion standard) in 161 journals published during 2000 (49,028 articles). RESULTS: Only 753 (1.5%) of the 49,028 articles were systematic reviews. The most sensitive strategy included five terms and had a sensitivity of 99.9% (95% confidence interval 99.6% to 100%) and a specificity of 52% (51.6% to 52.5%). The strategy that best minimised the difference between sensitivity and specificity had a sensitivity of 98% (97% to 99%) and specificity of 90.8% (90.5% to 91.1%). Highest precision for multiterm strategies, 57% (54% to 60%), was achieved at a sensitivity of 71% (68% to 74%). The term "cochrane database of systematic reviews.jn." was the most precise single term search strategy (sensitivity of 56% (52% to 60%) and precision of 96% (94% to 98%)). These strategies are available through the "limit" screen of Ovid's search interface for Medline. CONCLUSIONS: Systematic reviews can be retrieved from Medline with close to perfect sensitivity or specificity, or with high precision, by using empirical search strategies.

Information Storage and Retrieval↗

Systematic reviews of the effectiveness of quality improvement strategies and programmes.

Systematic reviews provide the best evidence on the effectiveness of healthcare interventions including quality improvement strategies. The methods of systematic review of individual patient randomised trials of healthcare interventions are well developed. We discuss methodological and practice issues that need to be considered when undertaking systematic reviews of quality improvement strategies including developing a review protocol, identifying and screening evidence sources, quality assessment and data abstraction, analytical methods, reporting systematic reviews, and appraising systematic reviews. This paper builds on our experiences within the Cochrane Effective Practice and Organisation of Care (EPOC) review group.

Canada↗

Systematic variation normalization in microarray data to get gene expression comparison unbiased.

Normalization removes or minimizes the biases of systematic variation that exists in experimental data sets. This study presents a systematic variation normalization (SVN) procedure for removing systematic variation in two channel microarray gene expression data. Based on an analysis of how systematic variation contributes to variability in microarray data sets, our normalization procedure includes background subtraction determined from the distribution of pixel intensity values from each data acquisition channel and log conversion, linear or non-linear regression, restoration or transformation, and multiarray normalization. In the case when a non-linear regression is required, an empirical polynomial approximation approach is used. Either the high terminated points or their averaged values in the distributions of the pixel intensity values observed in control channels may be used for rescaling multiarray datasets. These pre-processing steps remove systematic variation in the data attributable to variability in microarray slides, assay-batches, the array process, or experimenters. Biologically meaningful comparisons of gene expression patterns between control and test channels or among multiple arrays are therefore unbiased using normalized but not unnormalized datasets.

Algorithms↗

Advantage of systematic random ultrasound-guided biopsies, measurement of serum prostate-specific antigen level and determination of prostate volume in the early diagnosis of prostate cancer.

Two hundred and sixteen patients, presenting with a suspicious digital examination (stage T3 excluded) or a level of prostate-specific antigen (PSA) greater than or equal to 2.5 ng/ml, assessed by radioimmunoassay, underwent a transrectal ultrasound examination. Prostate volume was systematically calculated and correlated to PSA level. Biopsies were performed: (1) on suspicious peripheral hypoechoic areas; ultrasound-guided biopsies; (2) systematically on the 2 prostate lobes, whatever the result of transrectal ultrasound imaging:random systematic ultrasound-guided biopsies. In the 186 patients who had never undergone prostate surgery, ultrasound-guided biopsies showed 42 prostate cancers and random systematic ultrasound-guided biopsies showed 75; 14 of the 76 patients with normal digital rectal examination and transrectal ultrasound imaging had a prostate cancer. In the 30 patients who had previously undergone surgery for benign prostatic hypertrophy, random systematic ultrasound-guided biopsies showed 18 prostate cancers, 13% more than ultrasound-guided biopsies; 75% of patients with a serum PSA greater than 5 ng/ml had a prostate cancer. A very significant correlation was found between PSA level and prostatic volume (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, Neoplasm↗

Comment on the status of systematic desensitization.

Articles about systematic desensitization that appeared in mainstream behavior therapy journals between the years 1970 and 2002 were counted. Graphic displays of the data point to a sudden and lasting decline of interest in systematic desensitization among academics and researchers. A questionnaire concerning clinical use of orthodox systematic desensitization was mailed to 310 selected providers. Returns from 171 of those providers show that use of systematic desensitization has declined but continues to be fairly widespread. The decline of interest in systematic desensitization is explained: arguments are offered that revitalized interest would be beneficial but is not likely to occur.

Behavior Therapy↗

The application of the heuristic-systematic processing model to treatment decision making about prostate cancer.

The study investigated the utility of the Heuristic-Systematic Processing Model as a framework for the investigation of patient decision making. A total of 111 men recently diagnosed with localized prostate cancer were assessed using Verbal Protocol Analysis and self-report measures. Study variables included men's use of nonsystematic and systematic information processing, desire for involvement in decision making, and the individual differences of health locus of control, tolerance of ambiguity, and decision-related uncertainty. Most men (68%) preferred that decision making be shared equally between them and their doctor. Men's use of the expert opinion heuristic was related to men's verbal reports of decisional uncertainty and having a positive orientation to their doctor and medical care; a desire for greater involvement in decision making was predicted by a high internal locus of health control. Trends were observed for systematic information processing to increase when the heuristic strategy used was negatively affect laden and when men were uncertain about the probabilities for cure and side effects. There was a trend for decreased systematic processing when the expert opinion heuristic was used. Findings were consistent with the Heuristic-Systematic Processing Model and suggest that this model has utility for future research in applied decision making about health.

Adult↗

Investing in updating: how do conclusions change when Cochrane systematic reviews are updated?

BACKGROUND: Cochrane systematic reviews aim to provide readers with the most up-to-date evidence on the effects of healthcare interventions. The policy of updating Cochrane reviews every two years consumes valuable time and resources and may not be appropriate for all reviews. The objective of this study was to examine the effect of updating Cochrane systematic reviews over a four year period. METHODS: This descriptive study examined all completed systematic reviews in the Cochrane Database of Systematic Reviews (CDSR) Issue 2, 1998. The latest version of each of these reviews was then identified in CDSR Issue 2, 2002 and changes in the review were described. For reviews that were updated within this time period and had additional studies, we determined whether their conclusion had changed and if there were factors that were predictive of this change. RESULTS: A total of 377 complete reviews were published in CDSR Issue 2, 1998. In Issue 2, 2002, 14 of these reviews were withdrawn and one was split, leaving 362 reviews to examine for the purpose of this study. Of these reviews, 254 (70%) were updated. Of these updated reviews, 23 (9%) had a change in conclusion. Both an increase in precision and a change in statistical significance of the primary outcome were predictive of a change in conclusion of the review. CONCLUSION: The concerns around a lack of updating for some reviews may not be justified considering the small proportion of updated reviews that resulted in a changed conclusion. A priority-setting approach to the updating of Cochrane systematic reviews may be more appropriate than a time-based approach. Updating all reviews as frequently as every two years may not be necessary, however some reviews may need to be updated more often than every two years.

Bibliometrics↗

Methodological quality of systematic reviews of animal studies: a survey of reviews of basic research.

BACKGROUND: Systematic reviews can serve as a tool in translation of basic life sciences research from laboratory to human research and healthcare. The extent to which reviews of animal research are systematic and unbiased is not known. METHODS: We searched, without language restrictions, Medline, Embase, bibliographies of known reviews (1996-2004) and contacted experts to identify citations of reviews of basic science literature which, as a minimum, performed search of a publicly available resource. From these we identified reviews of animal studies where laboratory variables were measured or where treatments were administered to live animals to examine their effects, and compared them with reviews of bench studies in which human or animal tissues, cell systems or organ preparations were examined in laboratories to better understand mechanisms of diseases. RESULTS: Systematic reviews of animal studies often lacked methodological features such as specification of a testable hypothesis (9/30, 30%); literature search without language restriction (8/30, 26.6%); assessment of publication bias (5/30, 16.6%), study validity (15/30, 50%) and heterogeneity (10/30, 33.3%); and meta-analysis for quantitative synthesis (12/30, 40%). Compared to reviews of bench studies, they were less prone to bias as they specified the question (96.6% vs. 80%, p = 0.04), searched multiple databases (60% vs. 26.6%, p = 0.01), assessed study quality (50% vs. 20%, p = 0.01), and explored heterogeneity (33.3% vs. 2.2%, p = 0.001) more often. CONCLUSION: There seems to be a gradient of frequency of methodological weaknesses among reviews: Attempted systematic reviews of whole animal research tend to be better than those of bench studies, though compared to systematic reviews of human clinical trials they are apparently poorer. There is a need for rigour when reviewing animal research.

Animal Experimentation↗

The science of systematic reviewing studies of diagnostic tests.

BACKGROUND: Systematic reviews have gradually replaced single studies as the highest level of documented effectiveness of health care interventions. Systematic reviewing is a new scientific method, concerned with the development and application of methods for identifying relevant literature, analysing the material while increasing validity and precision, and presenting and discussing the results in a way that does justice to the research question and to the available evidence. The objective of this study was to review the systematic reviews in laboratory medicine, to evaluate the methods applied in these reviews and the applicability of guidelines of the Cochrane Methods Working Group on Screening and Diagnostic Tests, and identify areas for future research. METHODS: All the systematic reviews in the field of clinical chemistry and laboratory haematology that could be identified in Medline, EMBASE and other literature databases up to December 1998, were evaluated. RESULTS: We studied 23 reviews of diagnostic trials. Although all reviews share the same basic methodology, there was a wide variation in the methods applied. There was no consensus on the quality criteria for inclusion of primary studies. The results of the primary studies were heterogeneous in most cases. This was partly due to design flaws in the primary studies, but was also inherent in the diverse study designs in diagnostic trials. We observed differences in the analysis of the factors that cause heterogeneity of the results, and in the summary statistics used to pool the data from the primary studies. The additional diagnostic value of a test, after other test results are taken into consideration, was only addressed in one study. CONCLUSION: This overview of 23 reviews of diagnostic trials identifies areas in the methods of systematic reviewing where consensus is lacking, such as quality rating of primary studies, analysis of heterogeneity between primary studies and pooling of data. Guidelines need to be improved on these points.

Clinical Chemistry Tests↗

[Effects of systematic lymphadenectomy on length of survival in patients with gastric carcinoma].

INTRODUCTION: In the last few years there have been arguments between the Japanese and West European surgeons about benefits of systematic lymphadenectomies in surgery of gastric cancer. In this paper we would like to point out effects of systematic lymphadenectomies on survival of patients with gastric carcinoma. MATERIAL AND METHODS: This investigation included two groups of patients. The first group of 126 patients with gastric carcinoma underwent peritumor lymphadenectomy D1. The second group of 114 patients with gastric carcinoma underwent more radical types of lympadenectomy (D2, D2+, D3). Survival analysis included investigation of the following: 1. depth of tumor invasion, 2. metastatic involvement of the lymph nodes 3. tumor stage, 4. tumor recurrence. RESULTS: Most of examined patients presented with invasion and serosal and subserosal penetration (about 75% in both groups). More than 42% of lymph nodes had metastases and patients with systematic lymphadenctomy had better survival. Patients without subserosal invasion did not have metastatic lymph nodes in II, III, IV drianaged groups. There was no difference in regard to length of survival between the two analyzed group. 5-year survival rate was highest in stage I of gastric carcinoma (86%), but in stage IV 5-year survival rate was only 3.8%. Local recurrence (26%) and lymph node metastases (53%) were common causes of tumor recurrence in group with peritumor lymphadenectomy. In all groups of patients with advanced gastric cancer patients undergoing systematic lymphadenectomy presented with higher survival rate. DISCUSSION: Patients with advanced gastric cancer presented with higher number of metastatic lymph nodes in III and IV drainaged groups. In this stage systematic lympadenectomy played the main role. In the group of early gastric cancer there were no patients with metastatic lymph nodes in drainaged groups. CONCLUSION: D2 lympahedenectomy is a standard procedure for a great number of patients with gastric carcinoma, with high survival rate. Only in the group of advanced gastric cancer, patients undergoing more radical types of lymphadenectomies (D2+, D3) presented with better survival rates.

Carcinoma↗

Growth rate consists of baseline and systematic deviation components in Thoroughbreds.

The objective of this study was to establish a procedure for differentiating a baseline curve from a systematic deviation in weight-age data, and hence to develop a physiological growth model for the Thoroughbred. A total of 2,698 records for 175 foals was obtained during a period of 8 yr (1994 to 2001). Weight-age data were fit with a sigmoid growth equation, W = A(1 + be(-kt))M, where W is BW at age t, A is the asymptotic value of W, b is a scaling parameter that defines the degree of maturity at t = 0, k is a rate constant, and M defines the point of inflection in the sigmoid curve in relation to age. Short-term systematic deviations in the weight-age data were identified by a goodness-of-fit procedure and illustrated in three-dimensional contour plots of the sigmoid equation parameters as they changed upon removal of selected subsets of the data. Based on features of the contour plots, a negative deviation between 210 and 420 d of age was set aside, with the remaining data establishing the baseline data set. The sigmoid growth equation was fit to the baseline data set using a nonlinear mixed model with repeated measures, and indicated a mature weight of 542 +/- 6.2 kg reached at 7 yr. The systematic deviation identified in this weight-age data set is present in other published Thoroughbred growth data and is likely to result in erroneous parameter estimates if not set aside before fitting sigmoid growth equations to the thus-modified weight-age data set. The techniques developed in this study enable identification of short-term systematic deviations in weight-age data and define a realistic baseline growth curve. Differentiation of these two components enables the development of a physiological model of growth that distinguishes between baseline growth and environmental influences, represented respectively, by the baseline curve and the systematic deviation.

Animals↗

Using systematic reviews in clinical education.

Traditional educational methods change clinical practice only with considerable effort and difficulty. In particular, the teaching of critical appraisal in the setting of journal clubs does not increase the amount of medical research read by trainees. Experiential learning theory, corroborated by the success of problem-based learning, encourages us to link learning to the numerous medical questions that physicians generate while providing patient care. Systematic reviews can link these questions with the results of research that would otherwise be difficult to locate, read, and appraise. Systematic reviews are a uniquely powerful mechanism for teaching, and they offer teachers a new opportunity to model rational and effective use of information. Systematic reviews should be made available at clinical sites for use during "teachable moments." Resistance to the use of systematic reviews can be reduced by using existing journal clubs to teach about the strengths and limitations of these reviews. The point that systematic reviews are meant to assist, not replace, clinical decision making deserves emphasis in such teaching.

Education, Medical↗

General deming regression for estimating systematic bias and its confidence interval in method-comparison studies.

BACKGROUND: Various forms of least-squares regression analyses are used to estimate average systematic error (bias) and its confidence interval in method-comparison studies. When assumptions that underlie a particular regression method are inappropriate for the data, errors in estimated statistics result. In this report, I present an improved method for regression analysis that is free from the usual simplifying assumptions and is generally applicable to linearly related method-comparison data. METHODS: Theoretical equations based on the Deming approach, further developed by physicists and extended herein, were applied to method-comparison data analysis. Monte Carlo simulations were used to demonstrate the validity of the new procedure and to compare its performance to ordinary linear regression (OLR) and simple Deming regression (SDR) procedures. RESULTS: Simulation studies included three types of data commonly encountered in method-comparison studies: (a) constant within-method SDs for both methods, (b) constant within-method CVs for both methods, and (c) neither SDs nor CVs constant for both methods. For all cases examined, OLR produced unreliable confidence intervals of the estimated bias. However, OLR point estimates of systematic bias were reliable when the correlation coefficient was >0.975. SDR produced reliable estimates of systematic bias for all cases studied, but the confidence intervals of systematic bias were unreliable when SDs of methods varied as a function of analyte concentration. CONCLUSION: Only iteratively reweighted general Deming regression produced statistically unbiased estimates of systematic bias and reliable confidence intervals of bias for all cases.

Albumins↗