Psychotic symptoms and emotional distress in patients with Guillain-Barré syndrome.

Psychological disturbances in 49 most severely compromised Guillain-Barré syndrome patients were prospectively studied by a semistructured interview and assessed by repeat psychiatric examination during the patients' stay in the neuro-intensive care unit (ICU). Additional information was obtained from attending physicians, nurses and relatives. Anxiety (82%), acute stress disorder, depressive episodes (67%) and brief reactive psychosis (25%) were observed, with oneiroid psychosis (14%) among the latter. Psychotic episodes were strongly associated (p < 0.001) with severe tetraparesis, artificial ventilation and multiple cranial nerve dysfunction. CSF protein concentration was also correlated with the occurrence of psychotic symptoms. Patients themselves experienced loss of communication to be the most difficult condition to cope with. Fifty-five percent explicitly felt reassured by the environment of the ICU and 90% described contact with relatives to be most helpful. Our data suggest that motor deprivation and loss of communication are the conditions most closely connected with the occurrence of psychotic symptoms. Therapeutically, continuous psychosocial support and psychopharmacological measures may both be valuable tools to ameliorate distress.

Components-of-variance models for random-effects ROC analysis: the case of unequal variance structures across modalities.

RATIONALE AND OBJECTIVES: Several of the authors have previously published an analysis of multiple sources of uncertainty in the receiver operating characteristic (ROC) assessment and comparison of diagnostic modalities. The analysis assumed that the components of variance were the same for the modalities under comparison. The purpose of the present work is to obtain a generalization that does not require that assumption. MATERIALS AND METHODS: The generalization is achieved by splitting three of the six components of variance in the previous model into modality-dependent contributions. Two distinct formulations of this approach can be obtained from alternative choices of the three components to be split; however, a one-to-one relationship exists between the magnitudes of the components estimated from these two formulations. RESULTS: The method is applied to a study of multiple readers, with and without the aid of a computer-assist modality. performing the task of discriminating between benign and malignant clusters of microcalcifications. Analysis according to the first method of splitting shows large decreases in the reader and reader-by-case components of variance when the computer assist is used by the readers. Analysis in terms of the alternative splitting shows large decreases in the corresponding modality-interaction components. CONCLUSION: A solution to the problem of multivariate ROC analysis without the assumption of equal variance structure across modalities has been provided. Alternative formulations lead to consistent results related by a one-to-one mapping. A surprising result is that estimates of confidence intervals and numbers of cases and readers required for a specified confidence interval remain the same in the more general model as in the restricted model.

Analysis of uncertainties in estimates of components of variance in multivariate ROC analysis.

RATIONALE AND OBJECTIVES: Solutions have previously been presented to the problem of estimating the components of variance in the general linear model used for multivariate receiver operating characteristic (ROC) analysis. The case where the variance components do not change across the modalities under comparison was first treated, followed by the case where they are permitted to change. No analysis of uncertainties in these estimates has been presented previously. MATERIALS AND METHODS: For the case where the variance components do not change across modalities, the "jackknife-after-bootstrap" resampling procedure can be used together with conventional linear propagation of variance to solve for the uncertainties in estimates of the components. For the case where the components are permitted to change across modalities, a slight elaboration of this procedure is presented. RESULTS: The approach was validated by Monte Carlo simulations, where uncertainties in estimates of the variance components calculated by the jackknife-after-bootstrap procedure were found to converge in the mean to the Monte Carlo results over many independent trials. The method is exemplified with data from a study of readers-with and without the aid of a computer-assist modality-given the task of discriminating benign from malignant masses in mammography. CONCLUSION: The present approach is relevant to a broad class of problems where estimates of multiple contributions to the variance observed in ROC assessment of diagnostic modalities are desired, in particular, for the assessment of multiple-reader studies of computer-aided diagnosis in radiology where the variance components may change across reading modalities (eg, unaided vs computer-aided reading).

A correlation of alpha-smooth muscle actin and invasion in micronodular basal cell carcinoma.

BACKGROUND: Actin is largely responsible for cell motility and is only sparsely found in normal epithelial cells. An altered expression of actin in some malignancies may facilitate aggressive invasion. Micronodular basal cell carcinoma (BCC) has been shown to require more surgical stages, wider tissue margins, and deeper defects for extirpation during Mohs micrographic surgery relative to nodular BCC. OBJECTIVE: To provide preliminary data regarding a possible correlation between alpha-smooth muscle actin (alpha-SMA) expression within the cells or stroma of micronodular BCC and aggressive invasion. In addition, the incidence of alpha-SMA expression in micronodular, morpheaform, and nodular BCC is evaluated. METHODS: Nine micronodular basal cell carcinomas (7 primary, 2 recurrent) were evaluated for neural invasion, depth of tissue invasion, and alpha smooth muscle actin antibodies. The presence of alpha-smooth muscle actin antibodies was assessed using immunoperoxidase staining and compared with 13 morpheaform (13 primary, 0 recurrent) and 12 nodular (12 primary, 0 recurrent). RESULTS: Six of the nine micronodular (67%), eight of the 13 morpheaform (62%), and 0 of the 12 nodular (0%) BCCs stained positive for alpha-SMA. Of the six micronodular BCCs that stained positive for alpha-SMA, three invaded the fascia or muscle and three displayed neural invasion. In contrast, of the three micronodular BCCs that stained negative for alpha-SMA, none invaded the fascia or muscle and only one exhibited neural invasion. CONCLUSION: Actin was present in 66% of micronodular, 62% of morpheaform, and 0% of nodular BCC. The presence of actin in micronodular BCC may be a marker for aggressive invasion.

Mechanisms of sunscreen failure.

Sunscreen is used as a primary strategy to prevent sunburn and later skin cancer. However, sunscreen use has paradoxically been associated with the increasing incidence of skin cancer. One explanation for this puzzling observation is sunscreen failure (sunburn in the setting of sunscreen). Our purpose was to evaluate mechanisms of sunscreen failure in a sunscreen-using population. We carried out an epidemiologic comparison of sunburned and nonsunburned beachgoers who used sunscreen. We found that men were less likely to use sunscreen than women (chi(2) = 11.3, df = 1, P = .001), and when it was used, men were less likely to apply sunscreen to all sunlight-exposed skin (chi(2) = 18.4, df = 1, P = .0001). Swimmers who used sunscreen were significantly more likely to be sunburned compared with nonswimming sunscreen users (Fisher exact test, df = 1). Sunscreen may fail to prevent sunburn if it is washed off during swimming or if it is not applied to all exposed skin. Epidemiologic studies that link sunscreen use to skin cancer should evaluate whether sunburn occurred in this setting.

Continuous versus categorical data for ROC analysis: some quantitative considerations.

RATIONALE AND OBJECTIVES: Several authors have encouraged the use of a quasi-continuous rating scale for data collection in receiver operating characteristic (ROC) curve analysis of diagnostic modalities, rather than rating scales based on five to seven ordinal categories or levels of suspicion. Although many investigators have gone over to this method, a discussion of the issues continues. The present work provides a quantitative analysis from the viewpoint of measurement science. MATERIALS AND METHODS: A simple model of the effect of data discretization or quantization on the measurement of the variance of noisy data was developed. Then Monte Carlo simulations of multiple-reader, multiple-case ROC experiments were performed and analyzed in terms of components-of-variance models to investigate the effect of data quantization in that more complex setting. RESULTS: For single-reader studies, discretization into five categories can reduce the precision of ROC measurements by a large amount. The effect may be attenuated in multireader studies. CONCLUSION: More precise measurements of diagnostic detection performance and thus more efficient use of resources are served by good measurement methods. These are promoted by the use of a quasi-continuous rating scale in ROC studies.

Basal cell carcinoma arising in a cleft lip repair scar.

BACKGROUND: A case of basal cell carcinoma (BCC) developing in the repair scar of a cleft lip is presented. OBJECTIVE: Primary BCCs arising in surgical scars are very rare and no known reported cases exist of a BCC developing in a surgically repaired cleft lip scar. METHODS: A 69-year-old white man presented with a 5 mm primary BCC on his upper lip at the site of his cleft lip repair scar. The diagnosis was made by a tangential biopsy that showed an ulcerated BCC. RESULTS: Review of the medical literature indicates that a scar may be an independent risk factor for developing BCC. CONCLUSION: BCC may rarely arise in a cleft lip repair scar.

Bilateral auricular squamous cell carcinomas with perineural invasion.

BACKGROUND: Bilateral squamous cell carcinoma (SCC) of the external ears is a rare phenomenon, and we are unaware of instances of bilateral perineural involvement. OBJECTIVE: To describe bilateral auricular SCCs, each with perineural invasion. METHODS: Case report and literature review. RESULTS: Histopathologic examination revealed perineural invasion in both tumors. CONCLUSION: This appears to be an unusual presentation of bilateral auricular SCCs with perineural invasion in an elderly immunocompromised patient.

Study design in the evaluation of breast cancer imaging technologies.

RATIONALE AND OBJECTIVES: Bringing a new imaging technology to market is a complex process. Beyond conceptualization and proof of concept, obtaining U.S. Food and Drug Administration (FDA) approval for clinical use depends on the documented experimental establishment of safety and efficacy. In turn, safety and efficacy are evaluated in the context of the intended use of the technology. The purpose of this study was to examine a conceptual framework for technology development and evaluation, focusing on new breast imaging technologies as a highly visible and current case in point. MATERIALS AND METHODS: The FDA views technology development in terms of a preclinical and four clinical phases of assessment. With a concept of research and development as a learning model, this phased-assessment concept of regulatory review against intended use was integrated with a five-level version of a hierarchy-of-efficacy framework for evaluating imaging technologies. Study design and analysis issues are presented in this context, as are approaches to supporting expanded clinical indications and new intended uses after a new technology is marketed. CONCLUSION: Breast imaging technologies may be intended for use as replacements for standard-of-care technologies, as adjuncts, or as complementary technologies. Study designs must be appropriate to establish claims of superiority or equivalence to the standard for the intended use. Screening technologies are ultimately judged on their demonstrated effectiveness in decreasing cause-specific mortality through early detection, but they may be brought to market for other uses on the basis of lesser standards of efficacy (eg, sensitivity, specificity, positive and negative predictive value, and stage of disease detected).

Feature selection and classifier performance in computer-aided diagnosis: the effect of finite sample size.

In computer-aided diagnosis (CAD), a frequently used approach for distinguishing normal and abnormal cases is first to extract potentially useful features for the classification task. Effective features are then selected from this entire pool of available features. Finally, a classifier is designed using the selected features. In this study, we investigated the effect of finite sample size on classification accuracy when classifier design involves stepwise feature selection in linear discriminant analysis, which is the most commonly used feature selection algorithm for linear classifiers. The feature selection and the classifier coefficient estimation steps were considered to be cascading stages in the classifier design process. We compared the performance of the classifier when feature selection was performed on the design samples alone and on the entire set of available samples, which consisted of design and test samples. The area Az under the receiver operating characteristic curve was used as our performance measure. After linear classifier coefficient estimation using the design samples, we studied the hold-out and resubstitution performance estimates. The two classes were assumed to have multidimensional Gaussian distributions, with a large number of features available for feature selection. We investigated the dependence of feature selection performance on the covariance matrices and means for the two classes, and examined the effects of sample size, number of available features, and parameters of stepwise feature selection on classifier bias. Our results indicated that the resubstitution estimate was always optimistically biased, except in cases where the parameters of stepwise feature selection were chosen such that too few features were selected by the stepwise procedure. When feature selection was performed using only the design samples, the hold-out estimate was always pessimistically biased. When feature selection was performed using the entire finite sample space, the hold-out estimates could be pessimistically or optimistically biased, depending on the number of features available for selection, the number of available samples, and their statistical distribution. For our simulation conditions, these estimates were always pessimistically (conservatively) biased if the ratio of the total number of available samples per class to the number of available features was greater than five.

Clinical management of the acute sunburn reaction.

Critical reviews of published human studies about pharmacologic agents used to treat the sunburn reaction show that systemic and topical corticosteroids have little or no clinically important effect on the sunburn reaction. Systemic and topical nonsteroidal anti-inflammatory drugs, when used at dosages to achieve optimal serum levels for anti-inflammatory effect, only result in an early and mild reduction of ultraviolet B-induced erythema. Due to the lack of demonstrated clinical efficacy of these and other medicines to eliminate sunburn or decrease healing time, we currently suggest conservative local symptomatic treatment with adequate pain control until the sunburn naturally resolves.

Dermatologist and electrologist perspectives on laser procedures by nonphysicians.

BACKGROUND: As hair removal technology continues to evolve and new equipment comes to market, conflicts may develop between dermatologists and electrologists regarding the professional control and use of these devices. METHODS: A total of 1004 Fellows of the American Academy of Dermatology and 719 electrologists from the southern United States were anonymously surveyed about clinical laser procedures (CLPs). RESULTS: Compared to electrologists, dermatologists were more likely to support clinical laser regulations that placed licensed physicians in control (P =.001) and preferred that a delegating physician be physically present on the premises when CLPs were performed (P =.001). If a laser device was invented for permanent hair removal that was identical to traditional needle/probe electrolysis in every respect except energy type ("laser fiberoptic probe," LFP), electrologists were more likely than dermatologists to support independent use of this device by electrologists (P =.001). A greater percentage of electrologists from Texas, a state without electrolysis licensing, were more likely to support the unlicensed use of the LFP and CLPs than electrologists from states requiring electrolysis licensing. CONCLUSIONS: These data are consistent with previously published literature and permit a greater understanding of the multiple attitudinal, regulatory, and ethical issues involved when considering delegated and independent CLPs by electrologists.

Components-of-variance models and multiple-bootstrap experiments: an alternative method for random-effects, receiver operating characteristic analysis.

RATIONALE AND OBJECTIVES: The purpose of this study was to develop an alternative approach to random-effects, receiver operating characteristic analysis inspired by a general formulation of components-of-variance models. The alternative approach is a higher-order generalization of the Dorfman, Berbaum, and Metz (DBM) approach that yields additional information on the variance structure of the problem. MATERIALS AND METHODS: Six population experiments were designed to determine the six variance components in the DBM model. For practical problems, in which only a finite set of readers and patients are available, six analogous bootstrap experiments may be substituted for the population experiments to estimate the variance components. Monte Carlo simulations were performed on the population experiments, and those results were compared with the corresponding multiple-bootstrap estimates and those obtained with the DBM approach. Confidence intervals on the difference of ROC parameters for competing diagnostic modalities were estimated, and corresponding comparisons were made. RESULTS: For mean values, the agreement of present estimates of variance structures with population results was excellent and, when suitably weighted and mixed, similar to or closer than that with the DBM method. For many variance structures, the confidence intervals in this study for the difference in ROC area between modalities were comparable to those with the DBM method. When reader variability was large, however, mean confidence intervals from this study were tighter than those with the DBM method and closer to population results. CONCLUSION: The jackknife approach of DBM provides a linear approximation to receiver-operating-characteristic statistics that are intrinsically nonlinear. The multiple-bootstrap technique of this study, however, provides a more general, nonparametric, maximum-likelihood approach. It also yields estimates of the variance structure previously unavailable.

Differential expression of the HHV-8 vGCR cellular homolog gene in AIDS-associated and classic Kaposi's sarcoma: potential role of HIV-1 Tat.

Human herpesvirus 8 (HHV-8) has been causally linked to Kaposi's sarcoma (KS). There is significant homology between some HHV-8 genes and cellular genes including D-type cyclin (vCYC), G protein coupled receptor (vGCR), macrophage inflammatory proteins (vMIP-I, vMIP-II), bcl-2 (vBCL2), interferon regulatory factor-1 (vIRF1), interleukin-6 (vIL6), and complement-binding protein (vCBP). In this study, we analyzed expression of these viral homologs and HIV-1 Tat by reverse-transcriptase polymerase chain reaction (RT-PCR) coupled with Southern blot hybridization in AIDS-KS (AKS) tissue, classic KS tissue(CKS), and peripheral blood mononuclear cells, and phorbol ester (TPA)-treated and untreated HHV-8 positive lymphoma cells (BCBL1). While vCYC (AKS 6 of 6; CKS 3 of 3), vMIP-I (AKS 5 of 6, CKS 3 of 3), vBCL2 (AKS 6 of 6; CKS 3 of 3), and vIRF1 (AKS 5 of 6, CKS 3 of 3) transcripts were detected in both AKS and CKS, vGCR and HIV-1 Tat were expressed only in AKS samples (vGCR: AKS 3 of 6, CKS 0 of 3; Tat: AKS 4 of 6, CKS 0 of 3). vMIPII, vCBP, and vIL6 expression were not detected in any KS samples. Since vGCR expression is limited to AKS, it is possible that vGCR is activated by HIV-1 Tat. These results suggest that HIV-1 Tat may contribute to AKS pathogenesis through the tumorigenic and angiogenic effects of vGCR.