Biomedical subjects
Publications and source records attributed to J Hilden.
We describe the Computer Icterus Program (COMIP), a computer-assisted diagnosis (CAD) program which is designed to facilitate the early choice of a diagnostic strategy in cases of jaundice. To anticipate transfer to other centres, the COMIP program offers facilities to make local adjustments for relative disease incidences and for laboratory data. This is a useful extension for CAD systems.
Some key issues in industrial and environmental health risk research and the ensuing political decision process are discussed, with particular emphasis on statistical trouble spots: the acceptable risk concept; the welfare of future generations; burden of proof; research priorities; public visibility of risk and benefits; statistical extrapolations; multiple testing. The "tiny thief" phenomenon, discussed in detail, is the paradoxical fact that an almost harmless chemical may steal more of our health than a grossly hazardous chemical because the former is allowed to operate over a disproportionately long time span before being detected, if ever. The difficulty of proving that something is safe is reviewed. Finally, it is urged that politicians be taught the facts of scientific, including statistical, life; likewise, scientists should be made aware of the nature of political decision processes. Otherwise scientists will emigrate from health hazard research into areas of science where equivocal results and political interference are less common.
Among the 56 risk factors (RF) in pregnant women, used by the Danish National Board of Health, those that can predict complicated delivery (CD) were identified. The significance of parity, maternal age, social class and civil status was also analysed. The material comprises a Danish county cohort of 4,102 deliveries. The 56 original RFs affected 56% of the population. Women (8.8%) with twin pregnancy, fetus in breech, footling and transverse lie, or having an elective cesarean section were analysed separately. The incidence of CD was otherwise 39%. Of all the women, 8.7% had only prepregnancy RFs with a CD rate of 52%; 19.2% had only pregnancy RFs other than special conditions mentioned with a CD rate of 52%; 3.6% had both prepregnancy and pregnancy RFs with a CD rate of 62%. When the special conditions separately analysed were included, 14 RFs of the original 56 were found to predict complicated delivery. These affected 40% of the population. Primiparity was also a RF. The conceptional age of a primipara raised the odds in favor of CD by a factor 1.09 for each year. Social class and civil status were of no significance for CD.
In this study, antenatal risk factors (RF) predicting perinatal morbidity and mortality (PMM) were identified among 56 RFs defined by the Danish National Board of Health. The association with parity, age, social class, civil status, complicated delivery was also analysed. The RFs predicting complicated delivery have been described in Part I (1). All events, both prenatal and during the perinatal period, in 4,138 infants borne by 4,102 women in an entire Danish district were analysed. The frequency of perinatal mortality was 0.8% and of perinatal morbidity, 12.7%. The original 56 RFs affected 56% of the population. Fourteen 'new' RFs among the original 56 RFs predicted PMM and affected 27% of the population. The prepregnancy RFs affected 4.5% of all women with singleton pregnancies and their infants had a PMM rate of 21%; the pregnancy RFs affected 18.1%, the PMM rate being 25%; 3.4% had both prepregnancy and pregnancy RFs, their PMM rate was 41%. Twin pregnancies occurred in 0.9%, with a PMM rate of 47%. Apart from these groups, the PMM rate was only 8%. Parity, social class and civil status were of no significance for PMM. Some delivery complications, termed labor RFs, raised the odds of PMM by a factor of 1.92.
A general population of 928 men and women aged 30, 40, 50 and 60 years participated in a health survey with emphasis on low back trouble (LBT). In all 135 variables were analysed to identify possible indicators for first-time experience and recurrence or persistence of LBT during a one-year follow-up. Stepwise logistic regression analyses were carried out to identify the most informative combinations of indicators for prediction of LBT. For men, a high risk for recurrence or persistence of LBT was associated with frequent LBT in the past, worsening of the LBT since its onset, sciatica and living alone. For women corresponding risk indicators were: recency of the last LBT episode, waking up during night because of LBT, aggravation of LBT when standing, rumbling of "the stomach" and smoking. The strongest risk indicators for first-time experience of LBT were epigastric pain, daily smoking and low isometric endurance of the back muscles. In addition, hospitalisations for whatever cause and a long distance from home to work showed predictive power for first-time LBT among gainfully employed participants. The results indicate that persons with either recurring or first-time LBT had more health problems and probably lived under a higher psycho-social pressure than those without LBT in the follow-up year.
We present a method for early differentiation between obstructive and non-obstructive jaundice. On the basis of 14 variables (clinical data and clinical chemical tests, all available within 48 h) a simple decision tree or flow chart has been constructed. The diagnostic yield was as follows: 857 of 982 consecutive jaundiced patients (87%) in a data base and 98 of 108 patients in an independent test sample (91%) were correctly classified. Decision trees for the differentiation between benign or malignant causes within the obstructive group and between acute or chronic causes within the non-obstructive group are also presented. The resulting four-way classification was correct for 77% of the patients in the data base and for 72% of the patients in the test sample. The decision trees are compared with previous methods founded on Bayes' rule and logistic discrimination. The decision trees enable a quick and reliable classification of jaundiced patients, thus providing a valid basis for rational planning of the further diagnostic study.
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This paper shows that an algorithm for differential diagnosis of jaundice developed in Denmark has been successfully transferred for use in a Swedish hospital. The algorithm, which is based on data from nearly 1000 patients, utilises 21 items of information from the medical history, physical examination and blood chemistry. The algorithm recognises four diagnostic groups: benign obstructive jaundice, malignant obstructive jaundice, acute non-obstructive jaundice, and chronic non-obstructive jaundice. To each item of information, a score is attached reflecting its weight of evidence. Summing the scores for the symptoms and signs that are present leads to a probabilistic statement about the diagnosis. Because of missing data in the Swedish patient material, three of the items were excluded from the original algorithm. Corrections were made for differences in the distribution of diseases. In reclassification of 985 Danish patients the modified algorithm's "best bid", i.e. the diagnosis given the highest probability, was correct in 78% of cases. More important, 93% of the cases given a "confident" diagnosis (probability greater than 0.80) were correct. The corresponding figures when the algorithm was applied to Swedish patients were 76% and 93%, respectively. In both series the predicted probabilities were matched by a corresponding proportion of actual diagnostic hits. It is concluded that the algorithm leads to reliable estimates of diagnostic probabilities in jaundice and that the algorithm seems to work well in Sweden also.
Originally published in 1984, the Copenhagen Pocket Chart for early differentiation between causes of jaundice has been tested with success in centres outside Denmark. Using a logistic discrimination model, it estimates probabilities of obstruction and non-obstruction in each case (and provides a further subdivision if desired). Here we evaluate its performance in the hands of young clinicians on a consecutive series of 173 jaundiced patients from two Danish hospitals. The chart performed as well as in the original series: confident diagnoses (probability greater than or equal to 0.80) were assigned to 124 patients; of these 115 proved correct (93%). In 46 patients diagnostic probabilities were less than 0.80, and 3 patients had an unknown cause of jaundice. There were 108 cases in which physician and chart were in agreement, both with a confident diagnosis, and only one of these cases was wrong. In one hospital, contributing 107 cases, each patient was independently examined by a medical student in addition to the physician's examination. Student performance was equally good, practically speaking, in particular when taking the scores on the chart into consideration. As to observer disagreement, the student and the physician typically differed on 0-2 of the chart's 21 items. In no case, however, did this lead to a confident obstructive diagnosis being changed into a confident diagnosis of non-obstruction, or vice versa.
The effect of a number of explanatory variables on the degree of physiological jaundice in mature infants was evaluated by multiple regression analysis. The sampling was designed so that comparisons could be made between siblings. We found an effect of gestational age, gender, infant nutrition, ABO incompatibility and induction of labour. Taking these factors into account we still found a highly significant correlation between the peak bilirubin levels of siblings. Whether this correlation is genetically or environmentally determined is not clear.
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It has been shown recently that the ratio of unidirectional tracer fluxes, passing in opposite directions through a membrane which has transport properties varying arbitrarily with the distance from a boundary, is independent of time from the very first appearance of the two outfluxes from the membrane. This surprising proposition has been proved for boundary conditions defining standard unidirectional fluxes, and then generalized to classes of time-dependent boundary conditions. The operational meaning of all the resulting theorems is that when any of them appear to be refuted experimentally, the presence of more than one parallel transport pathway (that is, of membrane heterogeneity transverse to the direction of transport) can be inferred and analyzed. Recent experimental data have been interpreted accordingly. However, the proofs of the theorems given so far have not taken into account the possibility of temporary capture of tracer at sites fixed in the membrane (including also entrances to microscopic culs-de-sac). The possible presence of such a process, which would not affect fluxes in the steady state, left a fundamental gap in the aforementioned inferences. It is shown here that all the theorems previously proved for the flux ratio under unsteady conditions remain valid when temporary capture of tracer is admitted, no matter how the rate of capture, and the probability distribution of residence times of tracer at capture sites, may depend on the distance from a membrane boundary. The validity of the aforementioned inferences from observed time-dependence of the flux ratio is thereby extended to a much wider class of membrane transport processes.
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Extensive clinical and clinical chemical information was collected from 1002 consecutive jaundiced patients. Initial selection of variables based on Chi 2-tests or Mann-Whitney U-test allowed the removal of 64 of the 107 variables originally collected. A further selection of variables was carried out using a modified version of Bayes' rule thus reducing the number of variables from 43 to 22. Of the 982 patients with a final diagnosis 743 patients (76%) could be classified correctly into one of 13 diagnostic categories. The Bayes' rule was also applied to a test group of a further 110 jaundiced patients and found to perform equally well: of 108 patients with a final diagnosis 81 (75%) were correctly classified. A comparison between the clinician's diagnosis and the computer-aided diagnosis according to Bayes' rule demonstrated agreement with regard to one of the 13 diagnostic alternatives in 734 patients (75%), of whom 81 patients were wrongly diagnosed. In the test group agreement upon diagnosis was found in 80 patients (74%). By plausibly combining the computer-aided and the clinician's preliminary diagnoses, more correct classifications were obtained than with either method alone. Many diagnostic modalities such as ultrasound examination, CT-scan, and direct cholangiography are at hand today for the differential diagnosis of jaundice. Computer-aided diagnosis using Bayes' rule has proved a reliable tool for the clinician and can be used in the planning of a diagnostic strategy for the individual jaundiced patient.
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Utility scales, as elicited by the usual methods, are personal and cannot be averaged across individuals. Unfortunately, the Maximum Expected Utility principle calls for such averaging whenever medical decisions affect several patients--as they generally do because of budget constraints--and whenever a patient's scale is uncertain, such as for a comatose patient. Interpretation of therapeutic trials is particularly problematic when examined in this light, as are psychiatric decisions involving mental incompetence. To overcome this deficiency, a supplementary equal-right-to-treatment principle seems necessary, but the proposals examined here clash with the patient's right to choose his own utility scale for valuation of prospective treatment outcomes. Perhaps the basic assumption that personal suffering cannot be measured on an interpersonal scale is too radical, but the counterproposal involves too many assumptions to appear convincing. These issues have received remarkably little attention, if any, in the medical decision making literature.