133 research outputs found
Pepsinogen A, pepsinogen C, and gastrin as markers of atrophic chronic gastritis in European dyspeptics
Serum levels of pepsinogen and gastrin are parameters that can be used as biomarkers for gastric mucosa. The aim of this study was to validate these serum biomarkers, that is pepsinogen A (PGA), pepsinogen C (PGC), PGA/PGC ratio, and gastrin, as screening tests for precancerous lesions: atrophic chronic gastritis (ACG) or Helicobacter pylori-related corpus-predominant or multifocal atrophy. The study population was comprised of a subsample of 284 patients from the 451 included in the Eurohepygast cohort, between 1995 and 1997. The concentrations of PGA, PGC, and gastrin were measured by radioimmunoassays. Histological diagnosis was the gold standard. Cut-off points were calculated using receiving operator characteristics (ROC) curves. Factors linked to variation of biomarkers were identified using multivariate linear regression. The mean of each biomarker in the sample was: PGA, 77.4 microg x l(-1); PGC, 13.2 microg x l(-1); PGA/PGC, 6.7; and gastrin, 62.4 ng x l(-1). For ACG patients, the areas under the PGA, PGC, PGA/PGC, and gastrin ROC curves were 0.55, 0.62, 0.73, and 0.58, respectively. The best cut-off point for PGA/PGC was 5.6, with sensitivity 65% and specificity 77.9%. For H. pylori-related corpus-predominant or multifocal atrophy, the areas under the respective ROC curves were 0.57, 0.67, 0.84, and 0.69. The best cut-off point for PGA/PGC was 4.7, with sensitivity 77.1% and specificity 87.4%. The results suggested that only the PGA/PGC ratio can be considered as a biomarker for precancerous lesions of the stomach, and may be useful as a screening test
Lewis antigen expression and other pathogenic factors in the presence of atrophic chronic gastritis in a European population
To study the relationship between Helicobacter pylori cagA and vacA status and the expression of Lewis (Le) antigens and between these characteristics and atrophic chronic gastritis (ACG), H. pylori infection was assessed by culture and by histologic and serologic tests, cagA and vacA were assessed by a polymerase chain reaction - based reverse hybridization assay, and bacterial Le expression was assessed by immunoblotting. ACG was any form of antral or fundic atrophy with or without intestinal metaplasia. Of the 215 isolates, 64% were cagA+and 100% were vacA+(s1m1, 42%; s1m2, 29%; s2m2, 29%; and s2m1, 0). Le typing of 155 isolates showed that 6 (4%) were Lex, 31 (20%) were Ley, 87 (56%) were Lex,yand 31 (20%) were neither Lexnor Ley. Two main clusters of isolates were identified by multiple correspondence analysis: s1a/m1/cagA+/Lex+/Ley+ (n = 44; 29.7%) and s2/m2a/cagA-/Ley+ or Lex-/Ley- (n = 29; 19.7%). Among patients with ACG, 54% of their isolates were from cluster slml/cagA+/Lex+/Ley+, which was associated with the presence of ACG (odds ratio, 7.4; 95% confidence interval, 1.5-37.0).To study the relationship between Helicobacter pylori cagA and vacA status and the expression of Lewis (Le) antigens and between these characteristics and atrophic chronic gastritis (ACG), H. pylori infection was assessed by culture and by histologic and serologic tests, cagA and vacA were assessed by a polymerase chain reaction--based reverse hybridization assay, and bacterial Le expression was assessed by immunoblotting. ACG was any form of antral or fundic atrophy with or without intestinal metaplasia. Of the 215 isolates, 64% were cagA(+) and 100% were vacA(+) (s1m1, 42%; s1m2, 29%; s2m2, 29%; and s2m1, 0). Le typing of 155 isolates showed that 6 (4%) were Le(x), 31 (20%) were Le(y), 87 (56%) were Le(x,y), and 31 (20%) were neither Le(x) nor Le(y). Two main clusters of isolates were identified by multiple correspondence analysis: s1a/m1/cagA(+)/Le(x)+/Le(y)+ (n=44; 29.7%) and s2/m2a/cagA(-)/Le(y)+ or Le(x)-/Le(y)- (n=29; 19.7%). Among patients with ACG, 54% of their isolates were from cluster s1m1/cagA(+)/Le(x)+/Le(y)+, which was associated with the presence of ACG (odds ratio, 7.4; 95% confidence interval, 1.5-37.0)
Tiled vaults in western Sicily. Originality and continuity of an imported building technique
Abstract
The search for alternatives to wood for floorings has led to very interesting experiments on
vaulted structures, with diffusion in specific areas. We analyze the Sicilian ones consisting of
three layers of tiles with plaster, introduced in the mid-eighteenth century, reinterpreted with the
local materials and building culture, with original and ingenious solutions as to seismicity of area.
The oldest examples in Palermo date back to the period following the earthquake of 1726,
considered a good solution because of their lightness and presumed monolithic structure, able to
reduce the pressure on walls.
This report is an assessment of this building system, that we found during many restoration
works. Totally ignored by official current technical culture, tiled vaults usually are demolished or
transformed into decorative ceilings. A comparative examination of several cases has enabled us
to properly assess the actual possibility for maintenance, rehabilitation or re-proposal, whilst
preserving the structural function
Evaluating non-randomised intervention studies
Background
In the absence of randomised controlled trials (RCTs), healthcare practitioners and policy-makers rely on non-randomised studies to provide evidence of the effectiveness of healthcare interventions. However, there is controversy over the validity of non-randomised evidence, related to the existence and magnitude of selection bias.
Objectives
To consider methods and related evidence for evaluating bias in non-randomised intervention studies.
Methods
1. Three reviews were conducted to consider:
empirical evidence of bias associated with non-randomised studies
the content of quality assessment tools for non-randomised studies
the use of quality assessment in systematic reviews of non-randomised studies.
These reviews were conducted systematically, identifying relevant literature through comprehensive searches across electronic databases, handsearches and contact with experts.
2. New empirical investigations were conducted generating non-randomised studies from two large, multicentre RCTs by selectively resampling trial participants according to allocated treatment, centre and period. These were used to examine:
systematic bias introduced by the use of historical and non-randomised concurrent controls
whether results of non-randomised studies are more variable than results of RCTs
the ability of case-mix adjustment methods to correct for selection bias introduced by non-random allocation.
The resampling design overcame particular problems of meta-confounding and variability of direction and magnitude of bias that hinder the interpretation of previous reviews.
Results
Empirical comparisons of randomised and non-randomised evidence
Eight studies compared results of randomised and non-randomised studies across multiple interventions using meta-epidemiological techniques. The studies reached conflicting conclusions, explicable by differences in:
whether data were sourced from primary studies or systematic reviews
consideration of meta-confounding
inclusion of studies of varying quality
criterion for classifying discrepancies in results.
The only deducible conclusions were (a) results of randomised and non-randomised studies sometimes, but not always, differ and (b) both similarities and differences may often be explicable by other confounding factors.
Quality assessment tools for evaluating non-randomised studies
We identified 194 tools that could be or had been used to assess non-randomised studies. Around half were scales and half checklists, most were published within systematic reviews and most were poorly developed with scant attention paid to principles of scale development.
Sixty tools covered at least five of six pre-specified internal validity domains (creation of groups, blinding, soundness of information, follow-up, analysis of comparability, analysis of outcome), although the degree of coverage varied. Fourteen tools covered three of four core items of particular importance for non-randomised studies (How allocation occurred? Was the study designed to generate comparable groups? Were prognostic factors identified? Was case-mix adjustment used?). Six tools were thought suitable for use in systematic reviews.
Use of quality assessment in systematic reviews of non-randomised studies
Of 511 systematic reviews that included non-randomised studies, only 169 (33%) assessed study quality. Many used quality assessment tools designed for RCTs or developed by the authors themselves, and did not include key quality criteria relevant to non-randomised studies. Sixty-nine reviews investigated the impact of quality on study results in a quantitative manner.
Empirical estimates of bias associated with non-random allocation
The bias introduced by non-random allocation was noted to have two components. First, the bias could lead to consistent over- or underestimations of treatment effects. This occurred for historical controls, the direction of bias depending on time trends in the case-mix of participants recruited to the study. Second, the bias increased variation in results for both historical and concurrent controls, owing to haphazard differences in case-mix between groups. The biases were large enough to lead studies falsely to conclude significant findings of benefit or harm.
Empirical evaluation of case-mix adjustment methods
Four strategies for case-mix adjustment were evaluated: none adequately adjusted for bias in historically and concurrently controlled studies. Logistic regression on average increased bias. Propensity score methods performed better, but were not satisfactory in most situations. Detailed investigation revealed that adequate adjustment can only be achieved in the unrealistic situation when selection depends on a single factor. Omission of important confounding factors can explain underadjustment. Correlated misclassifications and measurement error in confounding variables may explain the observed increase in bias with logistic regression, as may differences between conditional and unconditional odds ratio estimates of treatment effects.
Conclusions
Results of non-randomised studies sometimes, but not always, differ from results of randomised studies of the same intervention. Non-randomised studies may still give seriously misleading results when treated and control groups appear similar in key prognostic factors. Standard methods of case-mix adjustment do not guarantee removal of bias. Residual confounding may be high even when good prognostic data are available, and in some situations adjusted results may appear more biased than unadjusted results.
Although many quality assessment tools exist and have been used for appraising non-randomised studies, most omit key quality domains. Six tools were considered potentially suitable for use in systematic reviews, but each requires revision to cover all relevant quality domains.
Healthcare policies based upon non-randomised studies or systematic reviews of non-randomised studies may need re-evaluation if the uncertainty in the true evidence base was not fully appreciated when policies were made.
The inability of case-mix adjustment methods to compensate for selection bias and our inability to identify non-randomised studies which are free of selection bias indicate that non-randomised studies should only be undertaken when RCTs are infeasible or unethical
Indirect comparisons of competing interventions:In collaboration with the International Stroke Trial Collaborative Group
OBJECTIVES: To survey the frequency of use of indirect comparisons in systematic reviews and evaluate the methods used in their analysis and interpretation. Also to identify alternative statistical approaches for the analysis of indirect comparisons, to assess the properties of different statistical methods used for performing indirect comparisons and to compare direct and indirect estimates of the same effects within reviews. DATA SOURCES: Electronic databases. REVIEW METHODS: The Database of Abstracts of Reviews of Effects (DARE) was searched for systematic reviews involving meta-analysis of randomised controlled trials (RCTs) that reported both direct and indirect comparisons, or indirect comparisons alone. A systematic review of MEDLINE and other databases was carried out to identify published methods for analysing indirect comparisons. Study designs were created using data from the International Stroke Trial. Random samples of patients receiving aspirin, heparin or placebo in 16 centres were used to create meta-analyses, with half of the trials comparing aspirin and placebo and half heparin and placebo. Methods for indirect comparisons were used to estimate the contrast between aspirin and heparin. The whole process was repeated 1000 times and the results were compared with direct comparisons and also theoretical results. Further detailed case studies comparing the results from both direct and indirect comparisons of the same effects were undertaken. RESULTS: Of the reviews identified through DARE, 31/327 (9.5%) included indirect comparisons. A further five reviews including indirect comparisons were identified through electronic searching. Few reviews carried out a formal analysis and some based analysis on the naive addition of data from the treatment arms of interest. Few methodological papers were identified. Some valid approaches for aggregate data that could be applied using standard software were found: the adjusted indirect comparison, meta-regression and, for binary data only, multiple logistic regression (fixed effect models only). Simulation studies showed that the naive method is liable to bias and also produces over-precise answers. Several methods provide correct answers if strong but unverifiable assumptions are fulfilled. Four times as many similarly sized trials are needed for the indirect approach to have the same power as directly randomised comparisons. Detailed case studies comparing direct and indirect comparisons of the same effect show considerable statistical discrepancies, but the direction of such discrepancy is unpredictable. CONCLUSIONS: Direct evidence from good-quality RCTs should be used wherever possible. Without this evidence, it may be necessary to look for indirect comparisons from RCTs. However, the results may be susceptible to bias. When making indirect comparisons within a systematic review, an adjusted indirect comparison method should ideally be used employing the random effects model. If both direct and indirect comparisons are possible within a review, it is recommended that these be done separately before considering whether to pool data. There is a need to evaluate methods for the analysis of indirect comparisons for continuous data and for empirical research into how different methods of indirect comparison perform in cases where there is a large treatment effect. Further study is needed into when it is appropriate to look at indirect comparisons and when to combine both direct and indirect comparisons. Research into how evidence from indirect comparisons compares to that from non-randomised studies may also be warranted. Investigations using individual patient data from a meta-analysis of several RCTs using different protocols and an evaluation of the impact of choosing different binary effect measures for the inverse variance method would also be useful
Which claw-free graphs are perfectly orderable?
AbstractAn undirected graph is called perfectly orderable if the set of its vertices admits a linear order < such that no chordless path with vertices a, b, c, d and edges ab, bc, cd has a<b and d<c. We characterize claw-free perfectly orderable graphs by nine infinite families of forbidden induced subgraphs. This result generalizes the characterization of totally balanced matrices found by Anstee and Farber, Edmonds and Lubiw, and Hoffman, Kolen and Sakarovitch. Implicit in our argument is a polynomial-time algorithm that, given any claw-free graph G, either constructs a perfect order in G or finds one of the forbidden induced subgraphs in G
A characterization of non-negative greedy matrices
Given an ordering of the variables according to nonincreasing coefficients of the objective function , the nonnegative matrix A is said to be greedy if, under arbitrary nonnegative constraint vectors b and h, the greedy algorithm maximizes subject to . Extending a result of Hoffman, Kolen, and Sakarovitch for -matrices, we characterize greedy matrices in terms of forbidden submatrices, which yields polynomial recognition algorithms for various classes of greedy matrices. The general recognition problem for the existence of forbidden submatrices is shown to be NP-complete
Inertial sensors as measurement tools of elbow range of motion in gerontology
G Sacco,1–3,* JM Turpin,3,4,* A Marteu,5 C Sakarovitch,6 B Teboul,2 L Boscher,4,5 P Brocker,4 P Robert,1–3 O Guerin2,3,7 1Memory Center, Claude Pompidou Institut, Department of Geriatrics, University Hospital of Nice, Nice, France; 2Centre d’Innovation et d’Usages en Santé (CIU-S), University Hospital of Nice, Cimiez Hospital, Nice, France; 3CoBTeK Cognition Behaviour Technology EA 7276, Research Center Edmond and Lily Safra, Nice Sophia-Antipolis University, Nice, France; 4Rehabilitation Unit, Department of Geriatrics, University Hospital of Nice, Cimiez Hospital, Nice, France; 5Rehabilitation Unit, Department of Neurosciences, University Hospital of Nice, L’Archet Hospital, Nice, France; 6Department of Clinical Research and Innovation, University Hospital of Nice, Cimiez Hospital, Nice, France; 7Acute Geriatrics Unit, Department of Geriatrics, University Hospital of Nice, Cimiez Hospital, Nice, France *These authors contributed equally to this work Background and purpose: Musculoskeletal system deterioration among the aging is a major reason for loss of autonomy and directly affects the quality of life of the elderly. Articular evaluation is part of physiotherapeutic assessment and helps in establishing a precise diagnosis and deciding appropriate therapy. Reference instruments are valid but not easy to use for some joints. The main goal of our study was to determine reliability and intertester reproducibility of the MP-BV, an inertial sensor (the MotionPod® [MP]) combined with specific software (BioVal [BV]), for elbow passive range-of-motion measurements in geriatrics. Methods: This open, monocentric, randomized study compared inertial sensor to inclinometer in patients hospitalized in an acute, post-acute, and long-term-care gerontology unit. Results: Seventy-seven patients (mean age 83.5±6.4 years, sex ratio 1.08 [male/female]) were analyzed. The MP-BV was reliable for each of the three measurements (flexion, pronation, and supination) for 24.3% (CI 95% 13.9–32.8) of the patients. Separately, the percentages of reliable measures were 59.7% (49.2–70.5) for flexion, 68.8% (58.4–79.5) for pronation, and 62.3% (51.2–73.1) for supination. The intraclass correlation coefficients were 0.15 (0.07–0.73), 0.46 (0.27–0.98), and 0.50 (0.31–40 0.98) for flexion, pronation, and supination, respectively.Conclusion: This study shows the convenience of the MP-BV in terms of ease of use and of export of measured data. However, this instrument seems less reliable and valuable compared to the reference instruments used to measure elbow range of motion in gerontology. Keywords: reliability, intertester reproducibility, inclinomete
A characterization of non-negative greedy matrices
Given an ordering of the variables according to nonincreasing coefficients of the objective function , the nonnegative matrix A is said to be greedy if, under arbitrary nonnegative constraint vectors b and h, the greedy algorithm maximizes subject to . Extending a result of Hoffman, Kolen, and Sakarovitch for -matrices, we characterize greedy matrices in terms of forbidden submatrices, which yields polynomial recognition algorithms for various classes of greedy matrices. The general recognition problem for the existence of forbidden submatrices is shown to be NP-complete
Concrete constructors: oral history accounts of building work on a large, complex site in 1960s Britain
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