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Information systems and audit in antenatal care.

The obstetric record as initiated at the antenatal booking clinic essentially identifies the degree of risk engendered in that pregnancy so that consequent obstetric and paediatric management is tailored appropriately. Whether carried by the patient or based in the hospital with a summary carried by the patient (shared-care card), this record should be exhaustive, the emphasis being on quality, not quantity, of information recorded. To obviate human error in history-taking, patient management or record transcription, we believe on-line computerization of patient records with spin-off paperwork to be the only patient management system to fulfil the above criteria. User-friendly software can be designed with highly branching programmes which provide clinical action suggestions in high-risk cases. Various 'error traps' enhance the accuracy of information recorded. Such systems can be operated by medical and midwifery staff with minimal keyboard skills and are well accepted by patients and staff. Inexpensive and versatile microcomputer networks are excellent for such systems. The operational effects are discussed. Audit means different things to different people and one's view on the subject depends on which definition is selected. Obstetricians are quick to take credit for instituting audit in the form of local and national data collection exercises, such as statistics on perinatal mortality, birthweight, etc. While these exercises certainly constitute observational studies, they cannot be used to make conclusions about the quality of care. There is no sound inference that can be made from a review of information contained in amalgamated databases of hospital statistics. Audit, as properly defined, hinges on inference: the inference that the quality of care was or was not of a high standard. Descriptive statistics, therefore, can be used to generate hypotheses but should not be used as a form of audit, at least not in obstetrics. Auditing the quality of care involves a study of process. It therefore depends on the assumption that we know which practices maximize beneficial outcomes. This exercise is therefore only relevant when we have good evidence linking the process of care with these outcomes. In some cases the accepted standard against which the process of care can be compared is very obvious. In other cases, however, the accepted standard should itself be audited to ensure that it is based on sound evidence.

Confidentiality↗

Symposium on Target Organ Toxicity: cardiovascular system. The epidemiologic approach.

Epidemiological studies rarely provide unequivocal data on the effects of toxic substances on human health. Unlike experimental studies, pertinent variables frequently cannot be controlled and some are often unknown. Nevertheless, these limitations can be dealt with by various facets of an epidemiological investigation. These include, the choice of a study design, selection of controls or comparison populations, evaluation of available data, statistical analysis, and the drawing of appropriate inferences from the data. Among the special problems that might be encountered in studies of the effects of cardiotoxic substances are, difficulties in establishing diagnoses, errors in death certificates, observer errors in electrocardiographic interpretations, and taking into account the effects of various risk factors known to be implicated in the etiology of cardiovascular diseases. In spite of various methodological problems and certain inherent limitations of epidemiological studies, they can, when properly conducted, make significant contributions to knowledge of disease etiology and provide the means of reducing the risk of a disease, even when its etiology is not completely known.

Epidemiologic Methods↗

Clinical inference by nursing students and experienced nurses concerning harmful outcomes occurring after medication errors: a comparative study.

Clinical inference is part of the clinical decision-making process and precedes judgment and action. It is an integrated response to patient cues and other evidence and a necessary skill for all nurses. The purpose of this study was to compare undergraduate and graduate nursing students' use of clinical inference in rating harmful outcomes for patients occurring after medication errors. The Medication Error Outcome Scale, a simulation methodology using medication error vignettes, was used to compare undergraduate and graduate students' use of clinical inference. Kruskal-Wallis analysis of variance showed that there was a statistically significant difference (P = .04) among freshman, junior, senior, baccalaureate, and Master's students' use of clinical inference in regard to perceived harm occurring after a medication errors. Post hoc Mann-Whitney U tests indicated that senior and baccalaureate students' use of clinical inference differed significantly (P = .005). This study suggests that clinical experience shapes clinical inference.

Adult↗

Statistical analyses of enzyme inhibitor kinetics: a hierarchical model-dependent approach.

Inference of the nature of an enzyme inhibitor and calculations of inhibitor constants from linear plots are prone to be unreliable when experimental error is significant. This may be minimised by a method of statistical analysis using nonlinear regression methods and modelling using the variance ratio test of a hierarchy of models of inhibitor behaviour.

Computer Simulation↗

The influence of hierarchy on probability judgment.

Consider the task of predicting which soccer team will win the next World Cup. The bookmakers may judge Brazil to be the team most likely to win, but also judge it most likely that a European rather than a Latin American team will win. This is an example of a non-aligned hierarchy structure: the most probable event at the subordinate level (Brazil wins) appears to be inconsistent with the most probable event at the superordinate level (a European team wins). In this paper we exploit such structures to investigate how people make predictions based on uncertain hierarchical knowledge. We distinguish between aligned and non-aligned environments, and conjecture that people assume alignment. Participants were exposed to a non-aligned training set in which the most probable superordinate category predicted one outcome, whereas the most probable subordinate category predicted a different outcome. In the test phase participants allowed their initial probability judgments about category membership to shift their final ratings of the probability of the outcome, even though all judgments were made on the basis of the same statistical data. In effect people were primed to focus on the most likely path in an inference tree, and neglect alternative paths. These results highlight the importance of the level at which statistical data are represented, and suggest that when faced with hierarchical inference problems people adopt a simplifying heuristic that assumes alignment.

Adult↗

Towards causal inference in occupational cancer epidemiology--I. An example of the interpretive value of using local rates as the reference statistic.

A brief overview is made of the criteria currently applied for establishing causation in occupational cancer epidemiology, and further criteria or 'desiderata' are proposed. These supplement the present somewhat simplistic ones for 'sufficient evidence of carcinogenicity' advocated by the International Agency for Research against Cancer in their monograph series. A frequent cause of confounding, not always appreciated, is the limited choice of a reference population for the statistical analyses. The study population is often an industrial one with marked regional and urban biases, especially for some of the cancers under scrutiny: these biases can influence markedly the resultant Standardized Mortality Ratio (SMR) calculated, and thus lead to misleading conclusions. The British Rubber Manufacturers' Mortality Study, 1946-1980, provided an opportunity to extract the data set of one of the 13 factories involved. Both local and national death rates were applied as a reference, and the use of the former substantially reduced the high SMRs previously recorded for lung and stomach cancers. This emphasized the need for further analyses when making other internal comparisons in order to accommodate more of the 'desiderata' listed. Ultimately causation can be inferred only after weighing up all the evidence, and must be based on a 'balance of probabilities'.

Data Interpretation, Statistical↗

Haplotype and missing data inference in nuclear families.

Determining linkage phase from population samples with statistical methods is accurate only within regions of high linkage disequilibrium (LD). Yet, affected individuals in a genetic mapping study, including those involving cases and controls, may share sequences identical-by-descent stretching on the order of 10s to 100s of kilobases, quite possibly over regions of low LD in the population. At the same time, inferring phase from nuclear families may be hampered by missing family members, missing genotypes, and the noninformativity of certain genotype patterns. In this study, we reformulate our previous haplotype reconstruction algorithm, and its associated computer program, to phase parents with information derived from population samples as well as from their offspring. In applications of our algorithm to 100-kb stretches, simulated in accordance to a Wright-Fisher model with typical levels of LD in humans, we find that phase reconstruction for 160 trios with 10% missing data is highly accurate (>90%) over the entire length. Furthermore, our algorithm can estimate allelic status for missing data at high accuracy (>95%). Finally, the input capacity of the program is vast, easily handling thousands of segregating sites in > or = 1000 chromosomes.

Algorithms↗

(Unlearned) lessons from John Graunt and Kenneth Rothman: a "CLASSic" example.

This commentary reviews the work of John Graunt and Kenneth J. Rothman on statistical significance and the need for prespecification of study end points. The authors argue that it is dangerous to substitute oversimplifications based exclusively on whether a result has reached statistical significance for a rational process of causal inference. An example is given based on the Celecoxib Long-term Arthritis Safety Study.

Anti-Inflammatory Agents, Non-Steroidal↗

Statistical mechanics of the Bayesian image restoration under spatially correlated noise.

We investigated the use of the Bayesian inference to restore noise-degraded images under conditions of spatially correlated noise. The generative statistical models used for the original image and the noise were assumed to obey multidimensional Gaussian distributions, whose covariance matrices are translational invariant. We derived an exact description to be used as the expectation for the restored image by the Fourier transformation and restored an image distorted by spatially correlated noise by using a spatially uncorrelated noise model. We found that the resulting hyperparameter estimations for the minimum error and maximal posterior marginal criteria did not coincide when the generative probabilistic model and the model used for restoration were in different classes, while they did coincide when they were in the same class.

Journal Article↗

Components of the antigen processing and presentation pathway revealed by gene expression microarray analysis following B cell antigen receptor (BCR) stimulation.

BACKGROUND: Activation of naïve B lymphocytes by extracellular ligands, e.g. antigen, lipopolysaccharide (LPS) and CD40 ligand, induces a combination of common and ligand-specific phenotypic changes through complex signal transduction pathways. For example, although all three of these ligands induce proliferation, only stimulation through the B cell antigen receptor (BCR) induces apoptosis in resting splenic B cells. In order to define the common and unique biological responses to ligand stimulation, we compared the gene expression changes induced in normal primary B cells by a panel of ligands using cDNA microarrays and a statistical approach, CLASSIFI (Cluster Assignment for Biological Inference), which identifies significant co-clustering of genes with similar Gene Ontology annotation. RESULTS: CLASSIFI analysis revealed an overrepresentation of genes involved in ion and vesicle transport, including multiple components of the proton pump, in the BCR-specific gene cluster, suggesting that activation of antigen processing and presentation pathways is a major biological response to antigen receptor stimulation. Proton pump components that were not included in the initial microarray data set were also upregulated in response to BCR stimulation in follow up experiments. MHC Class II expression was found to be maintained specifically in response to BCR stimulation. Furthermore, ligand-specific internalization of the BCR, a first step in B cell antigen processing and presentation, was demonstrated. CONCLUSION: These observations provide experimental validation of the computational approach implemented in CLASSIFI, demonstrating that CLASSIFI-based gene expression cluster analysis is an effective data mining tool to identify biological processes that correlate with the experimental conditional variables. Furthermore, this analysis has identified at least thirty-eight candidate components of the B cell antigen processing and presentation pathway and sets the stage for future studies focused on a better understanding of the components involved in and unique to B cell antigen processing and presentation.

Algorithms↗

An introduction to multilevel regression models.

Data in health research are frequently structured hierarchically. For example, data may consist of patients nested within physicians, who in turn may be nested in hospitals or geographic regions. Fitting regression models that ignore the hierarchical structure of the data can lead to false inferences being drawn from the data. Implementing a statistical analysis that takes into account the hierarchical structure of the data requires special methodologies. In this paper, we introduce the concept of hierarchically structured data, and present an introduction to hierarchical regression models. We then compare the performance of a traditional regression model with that of a hierarchical regression model on a dataset relating test utilization at the annual health exam with patient and physician characteristics. In comparing the resultant models, we see that false inferences can be drawn by ignoring the structure of the data.

Bias↗

Probabilistic diagnosis using a reformulation of the INTERNIST-1/QMR knowledge base. I. The probabilistic model and inference algorithms.

In Part I of this two-part series, we report the design of a probabilistic reformulation of the Quick Medical Reference (QMR) diagnostic decision-support tool. We describe a two-level multiply connected belief-network representation of the QMR knowledge base of internal medicine. In the belief-network representation of the QMR knowledge base, we use probabilities derived from the QMR disease profiles, from QMR imports of findings, and from National Center for Health Statistics hospital-discharge statistics. We use a stochastic simulation algorithm for inference on the belief network. This algorithm computes estimates of the posterior marginal probabilities of diseases given a set of findings. In Part II of the series, we compare the performance of QMR to that of our probabilistic system on cases abstracted from continuing medical education materials from Scientific American Medicine. In addition, we analyze empirically several components of the probabilistic model and simulation algorithm.

Algorithms↗

Monitoring and analysis of outcome studies.

Monitoring technology appears to be advancing at a rare that exceeds our ability to assess its effectiveness. RCTs are often poorly designed and lacks statistical power. Even high-quality RCTs may not provide inferences that can be generalized across all patient populations. Alternative methods of technology assessment, such as closed claims analysis, meta-analysis, and statistical process control, also have limitations. PORTs using a standard model of combined techniques are beginning to solve some of the more common methodological problems. The future of technology assessment relies on the ability to conduct large-scale cohort studies from routine practice settings. In terms of intraoperative monitors, this may require production of a complete and valid database of all monitored variables that can compared to a complete and valid database of all monitored variables that can be compared to a complete and valid database of appropriate outcome indicators. National standard for collection of data need to be developed. At this time, professional societies should focus more on developing guidelines for technology assessment than on guidelines for technology utilization.

Cohort Studies↗

Time-dependent surgical outcomes following cauda equina syndrome diagnosis: comments on a meta-analysis.

STUDY DESIGN: In this Journal Club review, we critically examine the methodology and results of a recently published meta-analysis describing the time dependency of surgical outcomes associated with cauda equina syndrome (CES) diagnosis. OBJECTIVES: Our objectives are to clarify the strengths, weaknesses, and appropriate use of statistics regarding the findings of the previous publication. SUMMARY OF BACKGROUND DATA: Surgical outcomes from published reports are related to both preoperative conditions and the time between surgery and diagnosis of CES. METHODS: We reexamined many of the papers that were used to create the surgical outcomes data set, including the publications that supplied quantitative information for logistic regression. Of special focus were studies that contributed to the "less than 24 hours from diagnosis" data. The use of statistical parameters such as probabilities and odds ratios to infer possible future outcomes is also addressed to clarify the papers' interpretations. To support the overall limitations of their generalized findings, we conducted a power analysis, which highlights the lack of statistical strength in the resulting conclusions. RESULTS: The results of the initial work state that an advantage exists in treating patients within 48 hours in comparison to treating them during a period greater than 48 hours after the onset of CES symptoms. However, the authors also state that no difference exists between the effects of an early surgery (less than 24 hours) compared with a subsequent period between 24 and 48 hours after CES onset. Key elements of logistic regression and meta-analysis are used to refute specific aspects of their methodology as well as their clinical interpretation regarding acute intervention. CONCLUSIONS: We conclude that a flawed methodology and misinterpretation of results are reported, understating the value of early surgical intervention.

Humans↗

Ordered multiple-class ROC analysis with continuous measurements.

Receiver operating characteristic (ROC) curves have been useful in two-group classification problems. In three- and multiple-class diagnostic problems, an ROC surface or hyper-surface can be constructed. The volume under these surfaces can be used for inference using bootstrap techniques or U-statistics theory. In this article, ROC surfaces and hyper-surfaces are defined and their behaviour and utility in multi-group classification problems is investigated. The formulation of the problem is equivalent to what has previously been proposed in the general multi-category classification problem but the definition of ROC surfaces here is less complex and addresses directly the narrower problem of ordered categories in the three-class and, by extension, the multi-class problem applied to continuous and ordinal data. Non-parametric manipulation of both continuous and discrete test data and comparison between two diagnostic tests applied to the same subjects are considered. A three-group classification example in the context of HIV neurological disease is presented and the results are discussed.

AIDS Dementia Complex↗

Empirical statistical estimates for sequence similarity searches.

The FASTA package of sequence comparison programs has been modified to provide accurate statistical estimates for local sequence similarity scores with gaps. These estimates are derived using the extreme value distribution from the mean and variance of the local similarity scores of unrelated sequences after the scores have been corrected for the expected effect of library sequence length. This approach allows accurate estimates to be calculated for both FASTA and Smith-Waterman similarity scores for protein/protein, DNA/DNA, and protein/translated-DNA comparisons. The accuracy of the statistical estimates is summarized for 54 protein families using FASTA and Smith-Waterman scores. Probability estimates calculated from the distribution of similarity scores are generally conservative, as are probabilities calculated using the Altschul-Gish lambda, kappa, and eta parameters. The performance of several alternative methods for correcting similarity scores for library-sequence length was evaluated using 54 protein superfamilies from the PIR39 database and 110 protein families from the Prosite/SwissProt rel. 34 database. Both regression-scaled and Altschul-Gish scaled scores perform significantly better than unscaled Smith-Waterman or FASTA similarity scores. When the Prosite/ SwissProt test set is used, regression-scaled scores perform slightly better; when the PIR database is used, Altschul-Gish scaled scores perform best. Thus, length-corrected similarity scores improve the sensitivity of database searches. Statistical parameters that are derived from the distribution of similarity scores from the thousands of unrelated sequences typically encountered in a database search provide accurate estimates of statistical significance that can be used to infer sequence homology.

Animals↗

Genetic algorithm-based maximum-likelihood analysis for molecular phylogeny.

A heuristic approach to search for the maximum-likelihood (ML) phylogenetic tree based on a genetic algorithm (GA) has been developed. It outputs the best tree as well as multiple alternative trees that are not significantly worse than the best one on the basis of the likelihood criterion. These near-optimum trees are subjected to further statistical tests. This approach enables ones to infer phylogenetic trees of over 20 taxa taking account of the rate heterogeneity among sites on practical time scales on a PC cluster. Computer simulations were conducted to compare the efficiency of the present approach with that of several likelihood-based methods and distance-based methods, using amino acid sequence data of relatively large (5-24) taxa. The superiority of the ML method over distance-based methods increases as the condition of simulations becomes more realistic (an incorrect model is assumed or many taxa are involved). This approach was applied to the inference of the universal tree based on the concatenated amino acid sequences of vertically descendent genes that are shared among all genomes whose complete sequences have been reported. The inferred tree strongly supports that Archaea is paraphyletic and Eukarya is specifically related to Crenarchaeota. Apart from the paraphyly of Archaea and some minor disagreements, the universal tree based on these genes is largely consistent with the universal tree based on SSU rRNA.

Algorithms↗

Head and neck extranodal non-Hodgkin's lymphomas in Indian patients.

Though radiotherapy has traditionally been the treatment of the choice for the patients with localised extranodal lymphomas of the head and neck areas, its adequacy as the sole modality of treatment has come to be questioned. The disease is shown to relapse in other distant extranodal sites especially the gastrointestinal tract. The addition of systemic chemotherapy has been suggested. Fifty-five patients with localised head and neck extranodal lymphomas were treated at the Tata Memorial Hospital during the period 1976-1982, 35 with radiation therapy alone and 20 with combination therapy. The total survival at 5 years was 65% for patients treated with radiation alone and 85% for those treated with combination therapy. The 5 year disease-free survival dropped to 45% for the former group but was 74% for the latter group. This difference was statistically significant (p less than 0.01). We infer that localised extranodal lymphomas be regarded as a systemic disease and be treated by a multimodal approach.

Adolescent↗