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Interim analyses of survival data in cancer clinical trials.

It is common practice to undertake interim analyses of accumulating survival data in a cancer clinical trial while patient entry and/or follow-up is still in progress. The purpose of making an interim analysis is to stop the trial if a convincing treatment difference can be demonstrated. The main problem with repeated significance tests is that the more often one analyses accumulating data, the greater the probability of eventually obtaining a significant result, p < 0.05 say, even when there is in reality no treatment difference. To allow for repeated testing one must therefore choose a more stringent nominal significance level as a criterion for stopping the trial. Repeated significance tests are normally applied at equally spaced intervals, and the maximum number of tests is decided in advance. This paper presents and compares the properties of two simple and commonly applied strategies for undertaking interim analyses of accumulating survival data.

Clinical Trials as Topic↗

Learning curves and impact of psychomotor training on performance in simulated colonoscopy: a randomized trial using a virtual reality endoscopy trainer.

BACKGROUND: The aim of this study was to analyze the learning curve for the GI Mentor II endoscope trainer and to determine whether psychomotor training can contribute to an improvement in the performance of virtual colonoscopy. METHODS: To analyze the learning curve, 28 subjects were divided into three groups on the basis of their experience with gastrointestinal (GI) endoscopy: experienced surgeons (group 1, performed > 200 endoscopic procedures, (n = 8)) residents (group 2, performed < 50 endoscopic procedures, (n = 10)); and medical students (group 3, never performed GI endoscopy, (n = 10)). The participants were tested on the GI Mentor II virtual reality simulator 10 consecutive times. Assessment of the learning curve was based on the following three parameters: time used, number of punctured balloons, and number of wall collisions. In the second part of the study, 20 subjects who had never performed GI endoscopy were included. After performing a virtual colonoscopy, they were randomized to a group that received psychomotor training and a control group. Finally, all subjects performed a virtual colonoscopy. Assessment of endoscopic skills during the colonoscopy was based on nine parameters dealing with psychomotor skills. RESULTS: The learning curve for time expended reached a plateau after the second repetition for group 1 (Friedman's test, p < 0.05), after the fifth repetition for group 2 (p < 0.05), and after the seventh repetition for group 3 (p < 0.05). Experienced surgeons did not improve their scores for regarding number of balloons punctured or number of wall collisions (p > 0.05), indicating the absence of a learning curve for these parameters. Group 2 improved their scores up to the fourth and fifth repetitions, respectively (p < 0.05), and group 3 up to the fifth and seventh repetitions, respectively (p < 0.05). Experienced surgeons achieved the best performance, followed by group 2 and then group 3. The surgeons who had received psychomotor training performed the second virtual colonoscopy significantly faster than the control group (Mann-Whitney test, p < 0.001) and made significantly greater improvement in all other parameters as well. CONCLUSIONS: There were different learning curves for surgeons depending on their endoscopic background. The familiarization rate on the simulator was proportional to the endoscopic experience of the surgeons. Psychomotor training had a significant effect on the performance of a simulated colonoscopy.

Clinical Competence↗

Ambient light working times of visible light-cured restorative materials. Does the ISO standard reflect clinical reality?

OBJECTIVES: The aim of this study was to determine whether a custom built light box could reliably reproduce clinical conditions and whether the current ISO standard test for the working time of visible light cured (VLC) materials (ISO. Dental Resin-based Restorative Materials. ISO:4049, 1991) reflected clinical reality. METHOD: The ISO test requires a VLC material to remain homogenous after exposure to an 8 kLux light source for 60 s. The relationship between the intensity of ambient lighting and the working times of visible light-cured (VLC) restorative materials was investigated by exposing 23 different VLC composite resin materials to a range of light intensities and measuring the working time in seconds: (a) under clinical operating conditions; (b) in a custom light box at 24 kLux; and (c) at 8 kLux in the light box. Working times were determined by placing 0.06 g samples between two glass plates and gently rotating until clefts or voids appeared. RESULTS: Clinical lighting conditions (24 kLux) gave a mean working time of 54 s (s.d. 14 s). In the light box at 24 kLux the mean working time was 54 s (s.d. 11 s). At 8 kLux (under otherwise identical conditions) the mean working time was 162 s (s.d. 49 s). SIGNIFICANCE: A 24 kLux illuminance in the laboratory gives an optimal correspondence to operative lighting conditions. This is three times the lighting level required for ISO purposes, and gives more realistic working times.

Analysis of Variance↗

Multimedia and virtual reality techniques in the treatment of male erectile disorders.

The present study is based on the observation that computer-simulated reality applied by virtual reality (VR) methods may offer a new means of treating male erectile disorders. The experimental design was based on the theory of psychological development, supported by multimedia acoustic experience and clinical tests. The method involved the use of virtual reality equipment and specially designed CD-ROM programmes. Excluding 15% drop-outs, the success rate was 82% for male erectile disorders due to psychological factors and 84%, excluding 17% drop-outs, for combined factor disorders. Psychotherapy with VR seems to hasten the healing process and reduce drop-outs, suggesting that this method opens or consolidates new or rarely used brain pathways, facilitating the flow of new mnemonic associations that promote the satisfaction of natural drives.

Adult↗

Ecological validity of list-learning tests and self-reported memory in healthy individuals and those with temporal lobe epilepsy.

We evaluated in patients with temporal lobe epilepsy (TLE) and healthy volunteers whether list-learning tests of episodic verbal/figural memory and subjective self-reports reliably indicate "Memory in Reality" (MIR). MIR was assessed by the incidental memory of the neuropsychological test event one week after testing. Subjective Memory was assessed by a questionnaire (SMQ). Patients achieved poorer results than controls in all measures of memory. Correlation and multiple regression analysis indicates that list-learning is highly predictive regarding performance in MIR. MIR predominantly relied on verbal memory in patients and on visual/figural memory in controls. Subjective memory differentiated patients and controls but it correlated to MIR only in subjects with unimpaired memory. In conclusion, the data indicate a high ecological validity of list-learning paradigms and they seriously question the diagnostic value of self-reported memory. They also indicate that incidentally acquired knowledge might be differentially represented in patients with a memory disorder and healthy persons.

Adult↗

A pilot and feasibility study of virtual reality as a distraction for children with cancer.

OBJECTIVE: To pilot and test the feasibility of a novel technology to reduce anxiety and pain associated with an invasive medical procedure in children with cancer. METHOD: Children with cancer (ages 7-19) whose treatment protocols required access of their subcutaneous venous port device (port access) were randomly assigned to a virtual reality distraction intervention, a non-virtual reality distraction, or treatment as usual without a distraction. The researchers obtained assessments of the child's pain and anxiety from the parent, child, and unblinded nurses. Pulse rate was monitored throughout the procedure, and behavioral indices of distress were recorded, as observed by the researchers. RESULTS: Reductions in pain and anxiety were found for children who used the virtual reality distraction in comparison with the no distraction condition as evidenced by lower pulse rate and reports of pain by nurses. No significant differences were found for the non-virtual reality condition versus the no distraction condition on pulse rate. CONCLUSIONS: These findings suggest that virtual reality may be a useful tool for distraction during painful medical procedures, but further studies are needed to test potential efficacy and feasibility during other, more distressing medical procedures with larger sample sizes.

Adolescent↗

Reality monitoring in adults reporting repressed, recovered, or continuous memories of childhood sexual abuse.

People who report either repressed or recovered memories of childhood sexual abuse (CSA) may have deficits in reality monitoring--the process whereby one discriminates memories of percepts from memories of images. Using signal detection methods, the authors found that adults reporting either repressed or recovered memories of CSA were less able to discriminate between words they had seen from words they had imagined seeing than were adults reporting either never having forgotten their CSA or adults reporting no history of CSA. Relative deficits in the ability to discriminate percepts from images (i.e., low d') were apparent on only some tests. The groups did not differ in their criterion--response bias--for affirming having seen versus imagined stimuli.

Adult↗

Backpropagation and regression: comparative utility for neuropsychologists.

The aim of this research was to compare the data analytic applicability of a backpropagated neural network with that of regression analysis. Thirty individuals between the ages of 64 and 86 (Mean age = 73.6; Mean years education = 15.4; % women = 50) participated in a study designed to validate a new test of spatial ability administered in virtual reality. As part of this project a standard neuropsychological battery was administered. Results from the multiple regression model R(2) = .21, p < .28; Standard Error = 18.01) were compared with those of a backpropagated ANN (R(2) = .39, p < .02; Standard Error = 13.07). This 18% increase in prediction of a common neuropsychological problem demonstrated that an ANN has the potential to outperform a regression.

Aged↗

Allergy, intolerance, and other adverse reactions to foods.

Adverse reactions (sensitivity) to foods are categorized as either allergic (immunologic) or intolerance (nonimmunologic). Some medical conditions caused by intolerance reactions have immunologic features, but these have not adequately explained the basis of these conditions. Idiosyncratic, toxic, and anaphylactoid reactions may resemble allergic reactions clinically even though they are not based on specific immunologic events. Complaints about adverse reactions to foods are common but most cannot be reproduced by challenge studies. This fact reflects the transient nature of many of these reactions and should prompt the pediatrician to be objective when diagnosing chronic or persisting conditions. Without objectivity, dietary avoidance measures potentially can have profound nutritional and psychosocial consequences. Negative skin-prick tests with foods have a high negative predictive value to rule out IgE-mediated mechanisms being operative. Skin-prick testing with cow's milk and hydrolysate formulas is useful in distinguishing mild "topical reactors" from the more severe "systemic reactors" and in selecting "hypoallergenic" formulas for their management. However, the DBPCFC is the "gold standard" that helps distinguish between reality and strongly held erroneous beliefs. This diagnostic test has established cow's milk, egg, peanut, and soybean as the foods most commonly responsible for allergic and intolerance reactions in children. The principles of management of these food-related conditions are similar. However, each food presents unique management issues to the pediatrician.

Adolescent↗

Executive-frontal lobe cognitive dysfunction in schizophrenia: a symptom subtype analysis.

Impairment of executive-frontal lobe functioning, affecting the planning, initiation and regulation of goal-directed behavior, is a common cognitive deficit in schizophrenia. However, it is unclear if deficits in these frontal-lobe-mediated abilities are differentially expressed across clinical subgroups. We analyzed executive-frontal abilities in relation to symptom expression in 53 hospitalized schizophrenic patients. Patients were assigned to one of three subgroups based on rank order analysis of Brief Psychiatric Rating Scale factors: Withdrawal-Retardation, Reality Distortion and Conceptual Disorganization. Executive-frontal tests included Visual Search, Verbal Fluency, Verbal Series Attention, Trail Making - Part B, Symbol Digit, Hopkins Verbal Learning, Digit Span, Wisconsin Card Sorting, Stroop Color-Word and Attentional Capacity. The schizophrenia group showed significant deficits relative to healthy control subjects (n = 20) on all tests. Exploratory factor analysis of test scores revealed three factors: (i) Verbal Processing/Memory; (ii) Cognitive Flexibility/Attention; and (iii) Psychomotor Speed/Visual Scanning. The three symptom subgroups were differentially impaired on executive-frontal abilities: Withdrawal-Retardation on psychomotor speed, verbal fluency, working memory, visual search and cognitive flexibility; Conceptual Disorganization on attention; Reality Distortion on verbal memory. The results have implications for syndrome definition, pharmacological intervention and prediction of outcome in schizophrenia.

Adult↗

An investigation of the role of 'hypnosis', hypnotic susceptibility and hypnotic induction in the production of age regression.

In response to criticisms of the methodology of Barber's(1969)experiments, a 2x2 factorial design, varying hypnotic susceptibility and hypnotic treatment, was used to study the role of 'hypnosis' in the production of age regression by suggestion. Twenty subjects of high hypnotic susceptibility and 20 subjects of low hypnotic susceptibility were randomly allocated to one of two treatment conditions:hypnotic induction procedure or motivational instructions. Both treatments were followed by suggestions to regress to the age of seven years. Two measures of age regression were taken:the Draw-A-Man-Test and a subjective rating of the reality of the experience. The results showed significant effects of both variables, with high suceptibility and induction treatment producing better regression on both measures than low susceptibility and motivation treatment. Hypnotic susceptibility was the stronger of the two variables. The ranking of the four conditions corresponded with predictions of hypnotic depth from the state theory of hypnosis, but the findings were not inconsistent with the non-state theory. The drawings of all regressed groups were more mature than the norms for the age of seven and the drawings of a group of seven year old children.

Adult↗

When representations conflict with reality: the preschooler's problem with false beliefs and "false" photographs.

It has been argued that young preschoolers cannot correctly attribute a false belief to a deceived actor (Wimmer & Perner, 1983). Some researchers claim that the problem lies in the child's inadequate epistemology (Chandler & Boyes, 1982; Wellman, 1988); as such, it is specific to the child's theory of mind and no such problem should appear in reasoning about nonmental representations. This prediction is tested below in the "false photograph" task: here an actor takes a photograph of an object in location X; the object is then moved to location Y. Preschool subjects are asked: "In the picture, where is the object?" Results indicate that photographs are no easier to reason about than are beliefs. Manipulations to boost performance on the photograph task proved ineffective. Further, an explanation of the failure as a processing limitation having nothing to do with the representational nature of beliefs or photographs was ruled out. It is argued that young children's failure on the false belief task is not due to an inadequate epistemology (though they may have one) and is symptomatic of a larger problem with representations.

Child, Preschool↗

CerbB2 status in breast cancer: pathologic issues.

INTRODUCTION: CerbB2 status determination in breast cancer is currently performed for predictive and prognostic information. However, much has yet to be learned about the accuracy, reproducibility and clinical correlation of the different testing methods available today. This is a review of the testing methods commonly in use and their applications in the management of breast cancer. METHODS: A Medline search for review articles with keywords cerbB2, Her2 testing, immunohistochemistry (IHC), fluorescence in situ hybridisation (FISH) and breast cancer was done. Manual cross-referencing from the afore-mentioned articles and perusal of the package inserts, recommendations and manuals from the manufacturers of various commercially available test kits were also performed. RESULTS: The 2 main methods of testing in use in most routine laboratories are IHC and FISH on formalin fixed, paraffin embedded, breast cancer tissue. There is no single, universally accepted method and the plethora of testing and interpretative protocols has confounded the issue of clinical correlation of cerbB2 status with outcome and patient selection for therapy. The current consensus in the literature is leaning towards FISH; however, as pointed out in this paper, the use of FISH as a routine test in most diagnostic laboratories is not yet a reality mainly due to cost, technical and manpower constraints. In this regard, IHC is by default the preferred choice in many routine laboratories. CONCLUSION: Universal standardisation of testing methods for cerbB2 status determination, together with further clinical studies on the correlation of each method with outcome and response to therapy, will aid in the identification of the ideal method for stratifying patients with breast cancer into prognostic and optimal therapeutic groups.

Adult↗

A longitudinal study of the relation between language and theory-of-mind development.

Fifty-nine 3-year-olds were tested 3 times over a period of 7 months in order to assess the contribution of theory of mind to language development and of language to theory-of-mind development (including the independent contributions of syntax and semantics). Language competence was assessed with a standardized measure of reception and production of syntax and semantics (the Test of Early Language Development). Theory of mind was assessed with false-belief tasks and appearance-reality tasks. Earlier language abilities predicted later theory-of-mind test performance (controlling for earlier theory of mind), but earlier theory of mind did not predict later language test performance (controlling for earlier language). These findings are consistent with the argument that language is fundamental to theory-of-mind development.

Child Language↗

Dual coding: a cognitive model for psychoanalytic research.

Four theories of mental representation derived from current experimental work in cognitive psychology have been discussed in relation to psychoanalytic theory. These are: verbal mediation theory, in which language determines or mediates thought; perceptual dominance theory, in which imagistic structures are dominant; common code or propositional models, in which all information, perceptual or linguistic, is represented in an abstract, amodal code; and dual coding, in which nonverbal and verbal information are each encoded, in symbolic form, in separate systems specialized for such representation, and connected by a complex system of referential relations. The weight of current empirical evidence supports the dual code theory. However, psychoanalysis has implicitly accepted a mixed model-perceptual dominance theory applying to unconscious representation, and verbal mediation characterizing mature conscious waking thought. The characterization of psychoanalysis, by Schafer, Spence, and others, as a domain in which reality is constructed rather than discovered, reflects the application of this incomplete mixed model. The representations of experience in the patient's mind are seen as without structure of their own, needing to be organized by words, thus vulnerable to distortion or dissolution by the language of the analyst or the patient himself. In these terms, hypothesis testing becomes a meaningless pursuit; the propositions of the theory are no longer falsifiable; the analyst is always more or less "right." This paper suggests that the integrated dual code formulation provides a more coherent theoretical framework for psychoanalysis than the mixed model, with important implications for theory and technique. In terms of dual coding, the problem is not that the nonverbal representations are vulnerable to distortion by words, but that the words that pass back and forth between analyst and patient will not affect the nonverbal schemata at all. Using the dual code formulation, and applying an investigative methodology derived from experimental cognitive psychology, a new approach to the verification of interpretations is possible. Some constructions of a patient's story may be seen as more accurate than others, by virtue of their linkage to stored perceptual representations in long-term memory. We can demonstrate that such linking has occurred in functional or operational terms--through evaluating the representation of imagistic content in the patient's speech.

Cognition↗

Genetic testing for breast cancer susceptibility: frequency of BRCA1 and BRCA2 mutations.

Genetic testing for breast cancer susceptibility became a reality after two cancer predisposition genes, BRCA1 and BRCA2, were identified. Mutations in these two genes were predicted to account for 85% to 90% of hereditary breast and ovarian cancer syndromes. We present results of mutation analysis of the coding sequence of these two genes in 110 consecutive non-Jewish breast cancer patients with a positive family history of breast and/or ovarian cancer. The individuals were identified in various cancer risk evaluation centers in the country. Twenty-two (20%) mutations in the BRCA1 gene and 8 mutations (7%) in the BRCA2 gene were detected. We also analyzed 52 Ashkenazi Jewish breast cancer patients for mutations in the BRCA1 and BRCA2 genes. Eleven Jewish individuals (21%) carried either one of the two common mutations, 185delAG and 5382InsC, in the BRCA1 gene and 4 individuals (8%) had the 6174delT mutation in the BRCA2 gene. The frequency of mutations in BRCA genes in affected people in this ethnic group was not significantly different from the non-Jewish population. On further analysis, the data demonstrate that neither age of onset nor phenotype of the disease had any significant predictive value for the frequency of mutations in these genes. These data confirm the lower prevalence of mutations in either of the BRCA genes in clinical families when compared to high-risk families used for obtaining linkage data in a research setting.

Adult↗

Thinking within the box: The relational processing style elicited by counterfactual mind-sets.

By comparing reality to what might have been, counterfactuals promote a relational processing style characterized by a tendency to consider relationships and associations among a set of stimuli. As such, counterfactual mind-sets were expected to improve performance on tasks involving the consideration of relationships and associations but to impair performance on tasks requiring novel ideas that are uninfluenced by salient associations. The authors conducted several experiments to test this hypothesis. In Experiments 1a and 1b, the authors determined that counterfactual mind-sets increase mental states and preferences for thinking styles consistent with relational thought. Experiment 2 demonstrated a facilitative effect of counterfactual mind-sets on an analytic task involving logical relationships; Experiments 3 and 4 demonstrated that counterfactual mind-sets structure thought and imagination around salient associations and therefore impaired performance on creative generation tasks. In Experiment 5, the authors demonstrated that the detrimental effect of counterfactual mind-sets is limited to creative tasks involving novel idea generation; in a creative association task involving the consideration of relationships between task stimuli, counterfactual mind-sets improved performance.

Achievement↗

A demonstration of virtual reality in free-flying honeybees: Apis mellifera.

Two experiments are reported on virtual reality illusion in free-flying honeybees. In the first experiment, subjects are trained on a simultaneous discrimination between two colored targets, one of which contains a sucrose reward. The ability to be influenced by a virtual reality illusion was assessed during an extinction test in which the training stimuli were a mirage of those used during acquisition. The results indicate that the bees consistently attempt to land on the previously rewarded color despite the fact that it is not there. In a second experiment, bees were unable to discriminate between two simultaneously presented, identically colored targets--one of which was real, the other a mirage.

Animals↗