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A blood test for M.S., E-UFA test, was reviewed with statistical analysis. The test was positive in 18 out of 22 M.S. patients, negative in the controls and OND. The results confirm the validity of the test.
Cardiovascular tests (CT) of autonomic function and non-invasive ambulatory blood pressure (BP) and heart rate (HR) monitoring were performed in 17 patients with multiple system atrophy (MSA) (mean age 61 +/- 9 years) and in 12 healthy subjects matched for sex and age. CT showed severe autonomic dysfunction with orthostatic hypertension (OH) in eight patients with MSA (47%) (Group I). The remaining nine out of the 17 patients didn't show BP abnormalities during CT but an impaired HR reflex response was found (Group II). BP monitoring showed a reversed circadian BP rhythm in Group I with higher night-time than day-time values, a blunted circadian BP pattern in Group II and a normal day-night BP reduction in controls. Day-night HR reduction was poor in Group II and absent in Group I. Post-prandial hypotension was evaluated after a standard meal. In Group I systolic/diastolic BP fell within 30 minutes after meal (from 135 +/- 16/89 +/- 13 to 118 +/- 17/73 +/- 12 mmHg; p < 0.05) and after two hours had not returned to basal levels. In Group II a reduction of only systolic BP was found within 45 minutes after meal and persisted for one hour. OH clinically identifies a subgroup of MSA patients with a more severe BP dysregulation characterized by severe post-prandial hypotension and reversed circadian BP rhythm. CT and ambulatory BP monitoring are useful tools in identifying early stage of cardiovascular autonomic impairment.
The problem of multiple comparisons is discussed in the context of medical research. The need for more powerful procedures than classical multiple comparison procedures is indicated. To this end some new, general and simple procedures are discussed and demonstrated by two examples from the medical literature: the neuropsychologic effects of unidentified childhood exposure to lead, and the sleep patterns of sober chronic alcoholics.
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With the macrophage electrophoretic mobility (MEM) test of Field & Caspary, lymphocyte sensitization to thyroid antigen (F1-fraction) is demonstrable in all subjects--multiple sclerosis (MS) patients, those with other (destructive) neurological diseases (OND) and normals. The MEM-LAD test enables a further differentiation to be made in neurological patients compared ot normals: Linoleic acid inhibits the positive result by about 95 per cent in the case of MS, 58 per cent in normals and 45 per cent in OND. The high reduction appears to be a characteristic of MS. It is seen at all stages and in all forms of the disease and is not materially influenced by moderate immunosuppressive therapy. The mothers of MS patients show an intermediate result of about 78 per cent, suggesting a familial (genetic) background to the metabolic phenomenon described here; there is, however, evidence of an added exogenic factor for the development of the disease. The theoretical basis of the LAD test suggests further therapeutic trials of linoleic acid in treatment of MS.
Multiple-choice tests in pharmacology were carried out with students who had no previous experience in this kind of examination. The curriculum in pharmacology was divided into four parts. Each part was followed by a test consisting of 90 questions. A special arrangement was made for those students who voluntarily participated in all four tests during academic year. Pass marks in all four completed tests were considered equivalent to a successful outcome in the one oral examination which is, at present, obligatory. In order to encourage a high level of participation amongst the students, failure in one or more of the tests had no adverse consequences. As a result, a markedly increased attendance at lectures, as well as a positive feed back of information for the faculty, were ascertained and assessment of the efficiency of the teaching methods facilitated. Application of multiple choice tests to the teaching of Pharmacology to undergraduate students proved to be recommendable, both as a test procedure and of advantage in the actual learning process.
Multiple choice format pre- and post-tests have a high likelihood of being equivalent (i.e. parallel) if well-known guidelines are followed. In the absence of such guidelines for pre- and post-tests of problem-solving, the authors devised a simple method of creating problems that are likely to be equivalent. The method was employed with patient management problems (PMPs) and focuses on maintaining the same form or structure of the problems while making the problems appear different to the examinee. Such problems are 'isomorphic'. The equivalence or parallelism of 10 PMPs with their isomorphic counterparts was demonstrated. The method for creating isomorphic PMPs appears to be applicable for creating equivalent pre- and post-tests composed of problems other than PMPs.
Serial electrophysiologic testing of multiple drugs was performed in 21 patients with recurrent atrioventricular (AV) nodal reentrant paroxysmal supraventricular tachycardia (PSVT). All patients had reproducible sustained PSVT induced before drug administration. Serial daily PSVT induction was attempted after administration of i.v. ouabain (0.01 mg/kg) (16 patients), i.v. propranolol (0.1 mg/kg (17 patients), i.v. ouabain + propranolol (same dosages) (12 patients), i.v. procainamide (600-1000 mg) (17 patients) and oral quinidine (1600-2400 mg/day) (nine patients). In two of 21 patients (10%), no tested drug prevented induction of sustained PSVT. In 19 of 21 patients (90%), one or more drugs prevented induction of sustained PSVT: ouabain--seven patients, propranolol--seven patients, ouabain + propranolol--seven patients, procainamide--11 patients, quinidine--seven patients. The site of action of ouabain and/or propranolol was either the antegrade limb or the retrograde limb (RL) of the circus movement. The site of action of procainamide or quinidine was always the RL. These 19 patients were treated with oral drugs, based on results of serial testing. Eighteen patients were successfully followed for 6-50 months. In 13 of these 18 patients PSVT did not recur. Two patients (11%) had > 95% reduction in frequency of PSVT recurrences, and three (17%) did not respond to chosen oral drugs. Serial electrophysiologic testing of multiple drugs is feasible in patients with AV nodal reentrant paroxysmal tachycardia. Drug responses are variable. In most but not all patients, serial electrophysiologic testing defines effective prophylactic drug therapy. This method of defining prophylactic drug therapy appears most suitable for patients with poorly tolerated tachycardias that occur only sporadically.
For a half century, the hot bath test has been used as a "diagnostic test" in multiple sclerosis. The appearance of new neurological signs or aggravation of preexisting signs generally is transient, with resolution on return of body temperature to normal. We have observed four patients, however, with considerable and prolonged neurological debilitation after hot bath testing. We suggest caution in the application of such testing.
The significance of a lod score value of 3 is very difficult to assess in linkage studies between a genetic marker and a complex disease. One reason is that multiple tests may have been performed, voluntarily or otherwise. For the same disease, linkage may be tested by different laboratories with several markers under various genetic models and diagnostic schemes for the disease. In such a case, we show that the probability of getting a lod score value of 3 under independent transmission of the disease and the marker may be not negligible.
The increase in Shannon information available from a diagnostic test associated with grading of the test results into many outcomes, rather than simply positive or negative, was examined to determine its upper limit as the number of test outcomes is increased indefinitely. Numerical methods were employed to find the optimal locations of outcome boundaries when a single normally distributed test variable is classified into 2, 3, 4, 5, 6, 8, 14, or 20 outcome categories. In each case Shannon information was computed for values of prior probability between 0.01 and 0.99 and for distances between the means in diseased and nondiseased populations ranging from 0.5 to 5.0 standard deviations. There is an important improvement in Shannon information as the number of outcomes defined is increased, but the increment in information diminishes rapidly with each additional category. A 20%-30% increment in information may be achieved with three outcomes instead of two. A further important increase in information occurs with four to seven outcomes, but beyond this the increment in inforation is negligible. The findings were similar over a wide range of prior probabilities and distances between the means. The analysis was extended to the case of multiple nonindependent tests by demonstrating their application to a Fisher discriminant function incorporating such tests. It was concluded that for normally distributed test variables: grading of test results significantly improves the information content of both single and multiple tests; the value of information content for 8-20 outcomes represents very nearly the maximum information content of a test; there is little value in using more than five to seven test outcomes; multiple grading should not be neglected for discriminant functions.
The applied statistician often encounters the need to compare two or more groups with respect to more than one outcome or response. Several options are generally available, including reducing the dimension of the problem by averaging or summarizing the outcomes, using Bonferroni or other adjustments for multiple comparisons, or applying a global test based on a suitable multivariate model. For normally distributed data, it is well established that global tests tend to be significantly more sensitive than other procedures. While global tests have also been proposed for multiple binary outcomes, their properties have not been well studied nor have they been widely discussed in the context of clustered data. In this paper, we derive a class of quasi-likelihood score tests for multiple binary outcomes, and show that special cases of this class correspond to other tests that have been proposed. We discuss extensions to allow for clustered data, and compare the results to the simple approach of collapsing the data to a single binary outcome, indicating the presence or absence of at least one response. The asymptotic relative efficiencies of the tests are shown to depend not only on the correlation between the outcomes, but also on the response probabilities. Although global tests based on a multivariate model are generally recommended, our findings suggest that a test based on the collapsed data can maintain surprisingly high efficiency, especially when the outcomes of interest are rare. Data from several developmental toxicity studies illustrate our results.
The evaluation of diagnostic tests attempts to obtain one or more statistical parameters which can indicate the intrinsic diagnostic utility of a test. Sensitivity, specificity and predictive value are not appropriate for this use. The likelihood ratio has been proposed as a useful measure when using a test to diagnose one of two disease states (e.g. disease present or absent). In this paper, we generalize the likelihood ratio concept to a situation in which the goal is to diagnose one of several non-overlapping disease states. A formula is derived to determine the post-test probability of a specific disease state. The post-test odds are shown to be related to the pre-test odds of a disease and to the usual likelihood ratios derived from considering the diagnosis between the target diagnosis and each alternate in turn. Hence, likelihood ratios derived from comparing pairs of diseases can be used to determine test utility in a multiple disease diagnostic situation.
The purpose of this study was to analyze the utilization of multiple radiologic procedures ordered simultaneously for the same clinical problem. The method was a retrospective study of patients referred to an urban community hospital who had multiple radiologic tests ordered simultaneously before the referring physician reviewed any of the results. Utilization Findings Codes, beta versions II and III, of the American College of Radiology were applied. In- and outpatient charts were reviewed for initial indication, subsequent diagnosis, and treatment. Ninety-three patients had 214 radiologic examinations (2.3 per patient). Of the 214 total, 129 (60%) were retrospectively coded as inappropriate (beta II version). For 98 reports, the initial interpreting radiologist's coded 16% as inappropriate versus 55% when retrospectively coded by the authors (P < 0.0001). After applying the beta III version, 18% were coded as positive (and related to symptoms), 79% negative, and 3% equivocal. There were 161 (74%) examinations ordered by primary care physicians and 53 tests ordered by specialists. Using the beta III version, the negative rate for primary care physicians was 81 and 75% for specialists (P = 0.447). It was concluded that ordering multiple radiologic tests simultaneously on the same patient resulted in a high number of inappropriate procedures and negative results.
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Routine serial nonstress fetal heart rate testing was evaluated in 94 patients with multiple gestations (193 fetuses). Reactive testing was associated with an uncomplicated perinatal outcome in 89% of the cases. Nonreactive fetuses had a significantly higher incidence of perinatal morbidity, including fetal distress in labor (77.8%), asphyxia (48%), and intrauterine growth retardation (28%). Overall perinatal mortality (21/1000) was nearly comparable to that observed in singleton pregnancies. Nonreactive fetuses had a perinatal death rate that was more than six times that of the reactive ones (80/1000 versus 12/1000). Antepartum nonstress testing was found to be a highly reliable and predictive tool in the assessment of multiple gestations.
Field et al. have recently suggested a blood test for multiple sclerosis based on determination of the absolute electrophoretic mobility of erythrocytes alone and in the presence of linoleic acid (LA) or arachidonic acid (AA). We attempted to reinvestigate this phenomenon in an Italian population.
To evaluate diagnostic tests, one would ideally like to verify, for example, with a biopsy, the disease state of all subjects in a study. Often, however, no all subjects are verified. Previous methods for evaluation assume that the decision to verify depends only on recorded variables. Sometimes, particularly if the disease process is not well understood, the decision to verify may also depend on unrecorded variables related to disease. We propose a method to estimate the true- and false-positive rates of multiple tests while adjusting for the effect, on the decision to verify, of unrecorded variables related to disease. To put the estimates into a more usable form, we develop a simple algorithm for creating a receiver-operating curve which maximizes the true-positive rate, given the false-positive rate. We apply the methodology to data on the early detection of prostate cancer using ultrasonography, digital rectal exam, and prostate specific antigen.