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Misuse of statistical methods in Arthritis and Rheumatism. 1982 versus 1967-68.

Articles published in Arthritis and Rheumatism in 1982 were compared with those from 1967-68 to evaluate trends in statistical methods and in the quantity and character of statistical misuse. Results show that among articles in 1982 using statistics, 66% contained methodologic errors. The percentage was similar in 1967-68, although fewer articles used statistics. In 1967-68 the most common error was failure to identify the statistical method used, whereas in 1982 multiple testing errors predominated, specifically, use of the t-test to compare 3 or more groups and comparison of 2 groups on multiple variables. The availability of calculators and computers which readily perform complex data analysis may underly the emergence of multiple testing errors. To compare multiple groups, we suggest using analysis of variance instead of the t-test. To avoid multiple testing errors, we recommend limiting the number of tests performed, lowering the alpha (significance) level, or using multivariate techniques.

Arthritis↗

The effect of item feedback on multiple-choice test responses.

This study examines the effects of item feedback on multiple-choice test responses. In the first experiment, a positive effect was predicted under instructions advising a penalty for errors; a larger beneficial effect on female scores was expected, given the (presumed) tendency of female participants toward omission when uncertain. Feedback effects were either negligible or negative, and the expected interaction effect with gender was not found. The second experiment was a high-powered replication of the feedback effect on errors, controlling for participants' ability. The discussion takes into account other evidence to state that recommendations of providing item feedback in the context of testing are neither theoretically nor empirically founded.

Adult↗

A comparison of student performance in two parallel physiology tests in multiple choice and short answer forms.

Two parallel tests in physiology, one in multiple choice answer form and one in short answer form, were administered consecutively to a group of 104 students. The construction of the questions in the two papers and marking schedules were such that if the form of examination did not influence the students' performance, the scores obtained in the two papers could be expected to be closely similar. The results indicate that the form of the question influences the students' performance significantly. The short answer format offers certain advantages over the multiple choice format and it would appear that greater use should be made of this type of question in testing at medical schools.

Education, Medical, Undergraduate↗

[Experience with the written examination (multiple choice test) in the teaching of anatomy].

All students (400 each winter-term) receive extensive information at the beginning of the course "anatomical propedeutics": a timetable with recommendations for learning, a list of instructional objectives and of terminology and an instruction for that type of test, the students never had experienced before. Feed-back is given by computer-output containing comments on the objective related to a wrong answer and indicating sub-test scores. Correlation of scores with results in the following dissection course seems to be acceptable. Questions of the multiple-choice test were compared by pairs with questions asked for in confrontation with the anatomical object. A strong coherence was found in answering correctly the multiple choice questions and the related oral exam. Over-all experience with a multiple choice test administered in Austria for the first time was rather encouraging.

Anatomy↗

Antigen specific stimulation of immune responses during long-term repeated skin testing with multiple antigens.

Delayed-type hypersensitivity (DTH) skin testing as an assay of immune competence is a widely used technique. Accordingly, clinical situations frequently occur which require that skin tests be performed many times on the same patient. In the present investigation, in vivo and in vitro immune responses were studied over a 7-month period in 22 normal human volunteers, each of whom were skin tested 6 times at monthly intervals with multiple antigens. Patterns of responses to the 7 specific skin test antigens observed during repeated skin testing in vivo indicated non-significant, but detectable, declines in skin test reactivity to tetanus, diphtheria and streptococcus antigens and increases in reactivity to trichophyton, tuberculin, candida and proteus antigens. In vitro lymphocyte transformation assays (LTAs) of cell-mediated immune (CMI) activities revealed that repeated skin testing, e.g., 3-5 serial skin tests, induced significantly increased levels of CMI reactions with 3 of the 4 skin test antigens used as challenge antigens. Since no significant changes in in vitro CMI responses were detected using 3 control "non-skin test" antigens, the effects observed were confirmed to be antigen specific. Increased IgG antibody responses were detected for only the toxoid antigens during the skin testing period. For the group of 22 normal volunteers, positive statistical correlations were not observed between any individual skin test antigen and the immune reactions assayed specifically for that antigen, including DTH responses and levels of circulating antigen-specific antibodies. Short term differences were detected between tetanus, diphtheria and streptococcus antigens in their LTA response patterns.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Multiple-choice testing in anatomy.

An analysis of 596 multiple-choice questions (MCQs) on human anatomy given at three First Professional Examinations for medical students is reported. The MCQ paper at each examination was 200 items long and consisted of three item-types: A, K and T/F. Each A-type item comprised a stem and five options, only one of the latter being the correct or best answer. Items of the K-type consisted of a stem and four responses, any number of which may be correct. The T/F items were of the three-response kind, the available options being 'true', 'false' and 'don't know'. Test reliability was computed by internal analysis, using the Kuder-Richardson 20 formula. Measures of concurrent validity were obtained by correlating the scores in the MCQ papers with the overall outcome of the First Professional Examination. Indices of item facility, discrimination and abstention were calculated. The effects of item-type and the availability of the 'don't know' option on examinee performance were also determined. Reliability (alpha) and concurrent validity (Pearson r) coefficients in the ranges of 0.71-0.85 and 0.80-0.93 (P less than 0.05) respectively were recorded. Regression analysis revealed the MCQ papers to be less sensitive predictors of the aggregate performance than the essay papers. The proportion of highly discriminatory and excessively difficult items was highest for the K-type. When the same K-type questions were re-exhibited in the indeterminate format, the examinees performed significantly better. Higher scores were also recorded when candidates were required to respond to all the questions than when they were offered the 'don't know' option and the percentage gain was higher for the low-scoring examinees. The appropriateness of multiple-choice testing as a tool for assessing student achievement in human anatomy is discussed.

Anatomy↗

The multiple tasks test. Strategies in Parkinson's disease.

The clinical balance tests presently used cannot predict falls in Parkinson's disease (PD), perhaps because they probe fairly isolated "components" of postural control. The Multiple Tasks Test (MTT) is a new balance test that simultaneously assesses multiple components of postural control. We investigated whether this MTT can detect postural abnormalities in PD patients. Fifty young controls (mean age 27.6 years), 20 elderly controls (mean age 62.5 years), and 20 PD patients (mean age 61.8 years, mean Hoehn and Yahr stage 2.2) participated. The MTT consisted of eight separate tasks of increasing complexity, which were executed sequentially. These tasks were composed of several motor components (standing up, walking, avoiding obstacles, touching the floor, turning around, and sitting down) and one cognitive component (answering serial questions). Four additional components included carrying an empty or loaded tray, wearing slippery shoes, and reduced illumination. All components within each task had to be performed simultaneously or directly sequentially. Errors were defined as Hesitations (slowed performance) or Blocks (complete cessation), which were scored separately for execution of the motor and cognitive components. Speed of performance was not stressed, but we did measure the time taken to complete all tasks. The complete MTT was performed by all subjects, except for a subgroup of seven patients and seven elderly controls who performed a shortened version, with only three of the eight sequential tasks (simple, intermediate, and most difficult). The number of subjects that produced Hesitations or Blocks for the motor components differed between the three groups [two-way repeated measures MANOVA, F(2.7) = 20.56; P < 0.001], patients making more errors than young and elderly controls. Furthermore, the number of subjects that made motor errors increased as the tasks became more complex [F(2.7) = 6.69; P < 0.001]. This increase differed across the three groups [significant interaction effect; F(2.7) = 3.31; P < 0.001] because particularly patients produced motor errors during the more complex tasks. In both control groups, 62% performed all eight consecutive tasks without errors in the motor components. In contrast, only 8% of the patients completed all tasks without motor errors (log rank test, P < 0.0001). This difference between patients and controls disappeared if the cognitive component was also scored, because more controls made cognitive errors during complex tasks than patients. Controls apparently gave priority to execution of the motor components, which they performed significantly faster than the patients. Both patients and controls made more errors during the shortened MTT, suggesting that learning effects (gain in performance through practice) influenced performance on the complete test. The MTT is a new balance test that clearly discriminates between healthy subjects and PD patients. Unlike controls, PD patients lend less priority to motor tasks over cognitive tasks. In addition, impaired motor learning may partially explain the higher error rate in PD. Future studies must determine if impaired MTT performance can predict actual falls in daily life.

Adult↗

The dot plot. A starting point for evaluating test performance.

We suggest that evaluations of diagnostic tests start with dot plots that depict multiple test results over multiple clinical states. From this starting point we can calculate posttest probabilities for multiple clinical states at multiple test results. Also, we can project one subset of clinical states as "disease positive" and a second subset as "disease negative" to provide standard analyses such as likelihood ratios, relative operating characteristic curves, posttest/pretest probability plots, sensitivity, specificity, and predictive value. Finally, this starting point provides an excellent basis for comparing multiple studies of diagnostic performance. The advantages of dot plots are illustrated with data on serum ferritin levels over multiple clinical states.

Ferritins↗

Phase Transition of Wax Enabling CRISPR Diagnostics for Automatic At-Home Testing of Multiple Sexually Transmitted Infection Pathogens.

Sexually transmitted infections (STIs) significantly impact women's reproductive health. Rapid, sensitive, and affordable detection of these pathogens is essential, especially for home-based self-testing, which is crucial for individuals who prioritize privacy or live in areas with limited access to healthcare services. Herein, an automated diagnostic system called Wax-CRISPR has been designed specifically for at-home testing of multiple STIs. This system employs a unique strategy by using the solid-to-liquid phase transition of wax to sequentially isolate and mix recombinase polymerase amplification (RPA) and CRISPR assays in a microfluidic chip. By incorporating a home-built controlling system, Wax-CRISPR achieves true one-pot multiplexed detection. The system can simultaneously detect six common critical gynecological pathogens (CT, MG, UU, NG, HPV 16, and HPV 18) within 30&#xa0;min, with a detection limit reaching 10-18 M. Clinical evaluation demonstrates that the system achieves a sensitivity of 96.8% and a specificity of 97.3% across 100 clinical samples. Importantly, eight randomly recruited untrained operators performe a double-blinded test and successfully identified the STI targets in 33 clinical samples. This wax-transition-based one-pot CRISPR assay offers advantages such as low-cost, high-stability, and user-friendliness, making it a useful platform for at-home or field-based testing of multiple pathogen infections.

Sexually Transmitted Diseases↗

Tree-structured gatekeeping tests in clinical trials with hierarchically ordered multiple objectives.

This paper discusses a new class of multiple testing procedures, tree-structured gatekeeping procedures, with clinical trial applications. These procedures arise in clinical trials with hierarchically ordered multiple objectives, for example, in the context of multiple dose-control tests with logical restrictions or analysis of multiple endpoints. The proposed approach is based on the principle of closed testing and generalizes the serial and parallel gatekeeping approaches developed by Westfall and Krishen (J. Statist. Planning Infer. 2001; 99:25-41) and Dmitrienko et al. (Statist. Med. 2003; 22:2387-2400). The proposed testing methodology is illustrated using a clinical trial with multiple endpoints (primary, secondary and tertiary) and multiple objectives (superiority and non-inferiority testing) as well as a dose-finding trial with multiple endpoints.

Antihypertensive Agents↗

Empirical estimates of Bonferroni corrections for use in chromosome mapping studies with the BXD recombinant inbred strains.

Most chromosome mapping efforts with the BXD recombinant inbred (RI) strains involve comparisons between a trait of interest and each of a large number of marker loci for evidence of linkage. Such multiple tests or comparisons greatly increase the Type I error rate compared to the single-test situation. Perhaps the most direct way to obtain multiple-test error rates is to employ a Bonferroni correction, where the single-test alpha is multiplied by the number of independent (nonredundant) comparisons (k) to yield a multiple-test alpha that protects against even one fortuitous association with any of the markers. Several empirical estimates of k are discussed for the published BXD marker set of 142 mapped loci and the newer unpublished marker set (October 1991) comprised of 352 marker loci. Reasonable estimates of k appear to be roughly 40 and 65 for these two marker sets, respectively.

Animals↗

Multiple antiphospholipid tests do not increase the diagnostic yield in antiphospholipid syndrome.

The family of antiphospholipid antibodies (aPL) includes a heterogeneous population of autoantibodies whose specificity is directed against not only phospholipids, but their complex with plasma proteins. Anticardiolipin antibodies (aCL) and lupus anticoagulant (LA) tests are widely performed to screen the aPL family which is associated with thrombotic complications in patients with systemic lupus erythematosus (SLE) or antiphospholipid syndrome (APS). The clinical significance of other aPL tests, including antibodies against phosphatidylserine (aPS), phosphatidylinositol (aPI), phosphatidic acid (aPA), phosphatidylcholine (aPC) and phosphatidylethanolamine (aPE), has not been established. The purpose of this study was to evaluate whether multiple aPL tests have enhanced diagnostic value for APS. We tested IgG/M/A aPS, aPI, aPA, aPC and aPE by ELISA using 10% bovine serum as blocking and sample diluent in 26 SLE patients with clinical manifestations of APS, but negative for both aCL and LA (Group 1). The results were compared with 32 SLE patients without any features of APS (Group 2) and 24 SLE patients with APS (aCL and/or LA positive) (Group 3). In Group 1, 1/26 (4%) was positive for IgA aPE, less frequent than in other groups, and none of the patients had any other aPL. In Group 2, 1/32 (3%) was positive for aPS, two (6%) for aPI, one (3%) for aPA and four (12.5%) for aPE. None was positive for aPC. In the third group, 13/24 (54%) were positive for aPS, 11 (46%) for aPI, 15 (63%) for aPA, four (17%) for aPC and seven (29%) for aPE. Since aPE was found in some patients, we extended the study, including 207 SLE patients, and tested aPE. IgG/M/A aPE was found in six (3%), 10(5%) and 21 (10%), respectively, but no association was found between aPE and any clinical features of APS. This study suggests that screening by multiple aPL tests does not increase the diagnostic yield in APS.

Adolescent↗

[Electrophysiological testing of multiple antiarrhythmic drugs in patients with paroxysmal supraventricular tachycardia after chronic oral administration].

Serial electrophysiological testing of multiple antiarrhythmic drugs was performed in 98 patients with paroxysmal supraventricular tachycardia (WPW syndrome 32, concealed WPW syndrome 46, atrioventricular nodal reentrant tachycardia 20). Of 32 patients with WPW syndrome, twelve patients had atrial fibrillation and atrioventricular reentrant tachycardia. Serial supraventricular tachycardia induction was attempted after chronic oral administration of verapamil (120-320 mg/day, 86 pts), diltiazem (180 mg/day, 10 pts), disopyramide (300-600 mg/day, 27 pts), propafenone (300-600 mg/day, 25 pts), flecainide (100-300 mg/day, 7 pts), SUN 1165 (150-300 mg/day, 10 pts), and combination therapy (18 pts) by using six polar electrode left in the heart in almost all patients. In 96 of 98 patients, one or more drugs prevented induction of SVT. Combination therapy alone was effective in 14 pts. The site of action of verapamil and diltiazem was antegrade and retrograde normal pathway AV conduction in circus movement. The site of action of disopyramide, propafenone, flecainide, SUN 1165 was antegrade and retrograde accessory pathway conduction and retrograde normal pathway conduction. Eighty two pts were successfully followed for 17.7 +/- 9.6 months. In 68 of these 82 pts, PSVT did not recur. Therefore, serial electrophysiological testing proved useful for the selection of prophylactic antiarrhythmic drugs.

Administration, Oral↗

Performance Tested Method multiple laboratory validation study of ELISA-based assays for the detection of peanuts in food.

Performance Tested Method multiple laboratory validations for the detection of peanut protein in 4 different food matrixes were conducted under the auspices of the AOAC Research Institute. In this blind study, 3 commercially available ELISA test kits were validated: Neogen Veratox for Peanut, R-Biopharm RIDASCREEN FAST Peanut, and Tepnel BioKits for Peanut Assay. The food matrixes used were breakfast cereal, cookies, ice cream, and milk chocolate spiked at 0 and 5 ppm peanut. Analyses of the samples were conducted by laboratories representing industry and international and U.S governmental agencies. All 3 commercial test kits successfully identified spiked and peanut-free samples. The validation study required 60 analyses on test samples at the target level 5 microg peanut/g food and 60 analyses at a peanut-free level, which was designed to ensure that the lower 95% confidence limit for the sensitivity and specificity would not be <90%. The probability that a test sample contains an allergen given a prevalence rate of 5% and a positive test result using a single test kit analysis with 95% sensitivity and 95% specificity, which was demonstrated for these test kits, would be 50%. When 2 test kits are run simultaneously on all samples, the probability becomes 95%. It is therefore recommended that all field samples be analyzed with at least 2 of the validated kits.

Allergens↗

A comparison of multiple-choice tests and free-response tests in examinations of clinical competence.

This paper reports a study which compared the performance of different groups of students and doctors on identical and equivalent tests set in an objective-type format and in a free-response format. The tests were designed to ensure that the content was relevant to clinical practice at the hospital intern level. In all test situations candidates' scores were significantly higher in the objective tests than in the free-response tests. This difference was greater for the more junior and less competent students than for the more competent doctors. The cueing effect of the options was thought to be the main factor responsible for the difference in performance. The results of a questionnaire survey demonstrated that students were aware of the deficiencies in multiple-choice tests. A large majority of the students believed that the free-response tests gave a more accurate assessment of their clinical ability. It was found that in these tests, aimed at measuring aspects of clinical competence, multiple-choice questions appeared to overestimate the candidate's ability to an extent that made them less suitable than free-response questions for this purpose. It was also found that free-response tests, of the type used in this study, provide a suitable alternative to multiple-choice tests for use in the written section of clinical examinations. It was concluded that the written component of the final examination in the medical course should have a preponderance of free-response items over multiple-choice items.

Australia↗

Understanding endoluminal gastroplications: a histopathologic analysis of intraluminal suture plications.

BACKGROUND: Endoluminal gastroplication is used to treat GERD, with modest results. Little is known of the histologic reaction to endosutures. Thus, the histologic response to intraluminal plications at different penetration depths within the gastric wall was studied in an animal model. METHODS: Intraluminal gastroplications were performed through a laparotomy in 18 New Zealand rabbits. Three sets of everted plications were placed at different penetration depths in each stomach: submucosa (SMpl), muscularis propria (Mpl), and serosa (Spl). Animals were randomized to survival times of 3, 10, or 60 days (respectively, Groups I, II, and III). Plications were compared with a grade scale for each histologic healing phase and gross inspection. RESULTS: Fusion between folds was absent in all groups. Serosa differed from muscularis propria with respect to the proportion of samples with microscopic ischemia (67% vs. 8%; p = 0.015), remaining sutures in Group III (33% vs. 3%; p < 0.05 in a single test of significance, but correction for multiple testing removes this significance), and remaining plications in Group II (96% vs. 54%; p < 0.05 in a single test of significance, but correction for multiple testing removes this significance). All of the total and partial histologic scores for the corresponding healing phase in each group escalated with penetration depth. Overall comparison of the histologic scores showed a significant difference among the plications in the proliferation (Group II, p = 0.004) and maturation (Group II, p = 0.009) phases. Total scores also differed among the plications in Groups II (p < 0.001) and III (p < 0.001). Plications were absent in all of Group III, with Spl resulting only in a flat scar. CONCLUSION: Everted intraluminal gastroplications do not result in fusion between folds irrespective of suture-penetration depth. A flat scar is the final outcome and appears proportional to the amount of ischemia, foreign body reaction, and suture depth.

Anastomosis, Surgical↗