Evaluation of chemiluminescence, toluidine blue and histopathology for detection of high risk oral precancerous lesions: A cross-sectional study.

BACKGROUND: Early detection holds the key to an effective control of cancers in general and of oral cancers in particular. However, screening procedures for oral cancer are not straightforward due to procedural requirements as well as feasibility issues, especially in resource-limited countries. METHODS: We conducted a cross-sectional study to compare the performance of chemiluminescence, toluidine blue and histopathology for detection of high-risk precancerous oral lesions. We evaluated 99 lesions from 55 patients who underwent chemiluminescence and toluidine blue tests along with biopsy and histopathological examination. We studied inter-as well as intra-rater agreement in the histopathological evaluation and then using latent class modeling, we estimated the operating characteristics of these tests in the absence of a reference standard test. RESULTS: There was a weak inter-rater agreement (kappa < 0.15) as well as a weak intra-rater reproducibility (Pearson's r = 0.28, intra-class correlation rho = 0.03) in the histopathological evaluation of potentially high-risk precancerous lesions. When compared to histopathology, chemiluminescence and toluidine blue retention had a sensitivity of 1.00 and 0.59, respectively and a specificity of 0.01 and 0.79, respectively. However, latent class analysis indicated a low sensitivity (0.37) and high specificity (0.90) of histopathological evaluation. Toluidine blue had a near perfect high sensitivity and specificity for detection of high-risk lesions. CONCLUSION: In our study, there was variability in the histopathological evaluation of oral precancerous lesions. Our results indicate that toluidine blue retention test may be better suited than chemiluminescence to detect high-risk oral precancerous lesions in a high-prevalence and low-resource setting like India.

Polysomnographic identification of anxiety and depression using deep learning.

Anxiety and depression are common psychiatric conditions associated with significant morbidity and healthcare costs. Sleep is an evolutionarily conserved health state. Anxiety and depression have a bidirectional relationship with sleep. This study reports on the use of analysis of polysomnographic data using deep learning methods to detect the presence of anxiety and depression. Polysomnography data on 940 patients performed at an academic sleep center during the 3-year period from 01/01/2016 to 12/31/2018 were identified for analysis. The data were divided into 3 subgroups: 205 patients with Anxiety/Depression, 349 patients with no Anxiety/Depression, and 386 patients with likely Anxiety/Depression. The first two subgroups were used for training and testing of the deep learning algorithm, and the third subgroup was used for external validation of the resulting model. Hypnograms were constructed via automatic sleep staging, with the 12-channel PSG data being transformed into three-channel RGB (red, green, blue channels) images for analysis. Composite patient images were generated and utilized for training the Xception model, which provided a validation set accuracy of 0.9782 on the ninth training epoch. In the independent test set, the model achieved a high accuracy (0.9688), precision (0.9533), recall (0.9630), and F1-score (0.9581). Classification performance of most other mainstream deep learning models was comparable. These findings suggest that machine learning techniques have the potential to accurately detect the presence of anxiety and depression from analysis of sleep study data. Further studies are needed to explore the utility of these techniques in the field of psychiatry.

Management of the COVID-19-Infected Psychiatric Inpatients: Unique Infection Prevention Considerations and Evolving Strategies.

REASON FOR REVIEW: The COVID-19 pandemic has affected the way healthcare services are provided and created challenges to the delivery of behavioral health in the inpatient setting. Here, we present our front-line experience of infection prevention for the psychiatric patient in the COVID era. RECENT FINDINGS: There are unique challenges surrounding COVID-19 precautions within inpatient psychiatric settings. The challenges presented to psychiatric care by COVID-19 begin in the emergency department and follow the patient through the continuum of care once admitted to the facility. Unit infrastructure, patient population, treatment modalities, staffing considerations, and discharge planning are distinct instances where COVID-19 protocols that are well-suited for other hospital settings necessitate revision for psychiatric settings. SUMMARY: The purpose of this communication is to add to the current body of shared experience of infection prevention for the psychiatric patient in the COVID-19 era.

Lack of association of the APOE epsilon 4 allele with the risk of obstructive sleep apnea: meta-analysis and meta-regression.

STUDY OBJECTIVES: Reports on the association of polymorphisms in the gene encoding apolipoprotein E (APOE)--a vital macromolecule in cholesterol metabolism--with obstructive sleep apnea (OSA) have provided conflicting results. Our objective was to meta-analytically synthesize the existing evidence for the association of the APOE epsilon4 allele with the risk of OSA. DESIGN: Random effects meta-analysis and meta-regression. SETTING: Genetic epidemiological studies reporting the association of APOE epsilon4 allele with OSA susceptibility. PATIENTS OR PARTICIPANTS: Synthesis of APOE epsilon4 allele data from 6,508 subjects including 1,901 cases of OSA and 4,607 controls. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Eight studies were included in the random effects meta-analysis; the summary effect size measured as odds ratio (OR) for association of the APOE epsilon4 allele with the risk of OSA was found to be 1.13 (95% confidence interval 0.86-1.47). There was a statistically significant heterogeneity (I2 = 72%, P = 0.001) across study results that was not explained by the mean age, proportion of males, or the proportion possessing the APOE epsilon4 allele or when grouped based on the geographic location of the study. CONCLUSIONS: The hypothesis that the APOE epsilon4 allele may be causally associated with OSA cannot be supported on the basis of published literature.

Arbitrary units are a composite and useful measure of muscle sympathetic nerve activity.

In humans, the muscle sympathetic nerve activity (MSNA) signal is challenging to detect, record and analyze. Several methods exist that attempt to capture the latent construct of MSNA. We directly compared the performance of five MSNA parameters: burst frequency, burst incidence, median burst amplitude, arbitrary units (AU) and fractal dimension (FD). The MSNA signal was recorded in 33 subjects for approximately 30 min before, during and after the application of a graded cold pressor test stimulus at 18 degrees C, 10 degrees C and 2 degrees C in random order with an adequate wash-out period. Using coefficient of variation, Shannon's entropy and principal component analysis, we observed that these five parameters defined two physical and conceptual domains of MSNA-frequency and amplitude. Since AU combines information from both these domains, we observed that it explained maximum inter-subject and inter-experimental segment variation. FD did not explain the inter-subject variability and was identified as a unique parameter in the factor analysis. Epidemiological studies that attempt to quantify MSNA may consistently use AU as the parameter for quantification of MSNA.

A clinicopathological study of eyelid malignancies from central India.

BACKGROUND: Eyelid malignancies are completely treatable if detected early. The treatment depends on the invasiveness of the cancer which in turn depends on the type of malignancy. AIM: The aim of the study was to characterize the distribution of the types of eyelid malignancies in central India. SETTINGS AND DESIGN: The study was conducted in the Department of Plastic and Maxillofacial Surgery at a tertiary care hospital. MATERIALS AND METHODS: We report a series of 27 cases of eyelid malignancies. In the same case series, we also include a case of malignant hemangiopericytoma which is an extremely rare form of eyelid malignancy worldwide. STATISTICAL ANALYSIS: Depending on the underlying statistical distribution, either analysis of variance (ANOVA) or the Kruskal-Wallis (K-W) test was used to assess the differential distribution of these variables across the types of eyelid malignancies observed in this study. RESULTS: We observed that sebaceous cell carcinoma (approximately 37%) was almost as prevalent as basal cell carcinoma (approximately 44%) in the study subjects and had an earlier age of occurrence and a more rapid clinical course. CONCLUSIONS: Sebaceous cell carcinoma of the eyelid is almost as common as basal cell carcinoma in a large tertiary care centre in central India.

A simple method to combine multiple molecular biomarkers for dichotomous diagnostic classification.

BACKGROUND: In spite of the recognized diagnostic potential of biomarkers, the quest for squelching noise and wringing in information from a given set of biomarkers continues. Here, we suggest a statistical algorithm that--assuming each molecular biomarker to be a diagnostic test--enriches the diagnostic performance of an optimized set of independent biomarkers employing established statistical techniques. We validated the proposed algorithm using several simulation datasets in addition to four publicly available real datasets that compared i) subjects having cancer with those without; ii) subjects with two different cancers; iii) subjects with two different types of one cancer; and iv) subjects with same cancer resulting in differential time to metastasis. RESULTS: Our algorithm comprises of three steps: estimating the area under the receiver operating characteristic curve for each biomarker, identifying a subset of biomarkers using linear regression and combining the chosen biomarkers using linear discriminant function analysis. Combining these established statistical methods that are available in most statistical packages, we observed that the diagnostic accuracy of our approach was 100%, 99.94%, 96.67% and 93.92% for the real datasets used in the study. These estimates were comparable to or better than the ones previously reported using alternative methods. In a synthetic dataset, we also observed that all the biomarkers chosen by our algorithm were indeed truly differentially expressed. CONCLUSION: The proposed algorithm can be used for accurate diagnosis in the setting of dichotomous classification of disease states.

Insights into age- and sickle-cell-disease-interaction using principal components analysis.

BACKGROUND: In the context of sickle cell anemia, peripheral blood indexes provide key information that is also potentially influenced by age. Therefore, it is necessary to understand the extent and nature of interactions between sickle cell anemia and age, especially in situations where there is a high prevalence of sickle cell anemia. METHODS: In a cross-sectional study of 374 subjects with varying hemoglobin S (HbS) status, we characterized the interaction between age and sickle hemoglobin using principal components analysis. RESULTS: Factor analysis in subjects with hemoglobin AA identified three orthogonal factors--normal erythropoiesis, presence of thalassemia and the aggregability potential of the blood. These three factors were differentially associated with hemoglobin status. Age influenced the association of factors #2 and #3 with hemoglobin status. CONCLUSION: Our findings suggest that the interaction between age and hemoglobin status needs to be considered in both clinical and public health settings.

Association of umbilical cord blood lead with neonatal behavior at varying levels of exposure.

BACKGROUND: In the light of the ongoing debate about lowering the cut-off for acceptable blood lead level to <5 microg/dL from the currently recommended level of <10 microg/dL, we considered whether prenatal exposure to varying levels of lead is associated with similar or disparate effects on neonatal behavior. METHODS: Using Brazelton's Neonatal Behavioral Assessment Scale (NBAS), an epidemiological approach and robust statistical techniques like multivariate linear regression, logistic regression, Poisson regression and structural equations modeling analyses we estimated the simultaneous indirect effects of umbilical cord blood lead (CBL) levels and other neonatal covariates on the NBAS clusters. RESULTS: We observed that when analyzed in all study subjects, the CBL levels independently and strongly influenced autonomic stability and abnormal reflexes clusters. However, when the analysis was restricted to neonates with CBL <10 microg/dL, CBL levels strongly influenced the range of state, motor and autonomic stability clusters. Abnormal walking reflex was consistently associated with an increased CBL level irrespective of the cut-off for CBL, however, only at the lower cut-offs were the predominantly behavioral effects of CBL discernible. CONCLUSION: Our results further endorse the need to be cognizant of the detrimental effects of blood lead on neonates even at a low-dose prenatal exposure.

Loss of lag-response curvilinearity of indices of heart rate variability in congestive heart failure.

BACKGROUND: Heart rate variability (HRV) is known to be impaired in patients with congestive heart failure (CHF). Time-domain analysis of ECG signals traditionally relies heavily on linear indices of an essentially non-linear phenomenon. Poincaré plots are commonly used to study non-linear behavior of physiologic signals. Lagged Poincaré plots incorporate autocovariance information and analysis of Poincaré plots for various lags can provide interesting insights into the autonomic control of the heart. METHODS: Using Poincaré plot analysis, we assessed whether the relation of the lag between heart beats and HRV is altered in CHF. We studied the influence of lag on estimates of Poincaré plot indices for various lengths of beat sequence in a public domain data set (PhysioNet) of 29 subjects with CHF and 54 subjects with normal sinus rhythm. RESULTS: A curvilinear association was observed between lag and Poincaré plot indices (SD1, SD2, SDLD and SD1/SD2 ratio) in normal subjects even for a small sequence of 50 beats (p value for quadratic term 3 x 10-5, 0.002, 3.5 x 10-5 and 0.0003, respectively). This curvilinearity was lost in patients with CHF even after exploring sequences up to 50,000 beats (p values for quadratic term > 0.5). CONCLUSION: Since lagged Poincaré plots incorporate autocovariance information, these analyses provide insights into the autonomic control of heart rate that is influenced by the non-linearity of the signal. The differences in lag-response in CHF patients and normal subjects exist even in the face of the treatment received by the CHF patients.

Caffeine Awareness in Children: Insights from a Pilot Study.

STUDY OBJECTIVES: Caffeine, a commonly consumed psychoactive substance, can have significant effects on sleep. Caffeine intake among children is increasing, mainly in the form of sodas. However, adolescent caffeine consumers may lack knowledge about the caffeine content in common beverages. If true, this very fact may hamper the assessment of the effects of caffeine consumption on sleep in children if such assessments are a priori dependent on responders being able to reliably distinguish between caffeinated and noncaffeinated beverages. This preliminary study investigated adolescents' caffeine knowledge and intake at a Cleveland-area public middle school. METHODS: Seventh- and eighth-grade students were surveyed using: (1) the Caffeine Literacy and Sleep Study (CLASS), a 15-question pilot instrument designed to assess caffeine knowledge and intake by type, quantity and timing, as well as sleep habits; and (2) the Cleveland Adolescent Sleepiness Questionnaire (CASQ), a validated survey measuring excessive daytime sleepiness in adolescents. These questionnaires were distributed and collected during a specified class period. RESULTS: Of the 635 seventh- and eighth-grade students who attended school on the day of the study, 555 (87%) participated. Lack of knowledge about caffeine content of particular drinks was noted in seventh and eighth graders of both sexes with nearly 29% unaware that their favorite drinks contain caffeine and more than 50% unable to correctly identify the drinks with the most caffeine. A low percentage of students correctly identified light-colored sodas lacking caffeine: 7-Up (24.1%), Sierra Mist (38.9%), ginger ale (39.8%), Sprite (39.8%), and Fresca (53.7%). The percentages of students correctly identifying caffeinated light-colored beverages were: Arizona Green Tea (43.5%), Mello Yellow (50.9%), and A&W cream soda (67.6%). However, Mountain Dew was correctly identified by most (93.5%) as caffeinated. CONCLUSIONS: Students were not consistently able to identify caffeine content or lack thereof in some common beverages. The results of this pilot study show that caffeine literacy in adolescents warrants further investigation and educational intervention.

In vitro effect of over-the-counter probiotics on the ability of Candida albicans to form biofilm on denture strips.

PURPOSE: There is a burgeoning recognition and interest in the potential of probiotics in the treatment and prevention of oral candidiasis associated with the use of dentures. Our aim was to investigate if commercially available over-the-counter probiotics can influence the ability of Candida albicans to form biofilms, which is considered a hallmark of the initiation and progression of oral candidiasis. METHODS: We conducted a 2×5 factorial in vitro study to culture C. albicans on denture strips and challenge with one of the following four commercially available probiotics in bacterial or cell-free supernatant form: Accuflora®, Align®, Culturelle® and Sustenex®. C. albicans biofilm formation was studied in triplicates in all factorial combinations of the study and assessed qualitatively with fluorescence microscopy and quantitatively with tetrazolium salt (XTT) reduction assay. Quality control measures included determination of coefficient of variation, Bland Altman plots and Pittman's test. Results were analyzed using two-way analysis of variance (ANOVA) with pairwise post-hoc Scheffe's tests. RESULTS: Our experimental conditions passed the quality control checks. Two-way ANOVA results indicated that cell-free supernatants provided a stronger and significant inhibitory effect on biofilm formation than their bacterial counterparts (2-way ANOVA p=3.8×10(-6)). Further, Lactobacillus-containing probiotic formulations (Accuflora® and Culturelle®) significantly reduced biofilm formation especially in supernatant form. CONCLUSION: Commercially available probiotics that contain Lactobacilli species interfere with the in vitro ability of C. albicans to form biofilms on dentures. The mechanistic and clinical implications of our results need to be addressed by larger in vivo studies.

Association of plasma homocysteine with self-reported sleep apnea is confounded by age: results from the national health and nutrition examination survey 2005-2006.

High levels of plasma homocysteine are implicated in the pathogenesis of cardiovascular diseases especially if accompanied by sleep apnea, but a direct pathogenetic link between plasma homocysteine levels and obstructive sleep apnea is debatable. This association can have far-reaching public health implications considering the inverse association between folate and plasma homocysteine. We used data from the 2005-2006 cycle of the National Health and Nutrition Examination Survey (NHANES) to test the hypothesized associations. Of the 4490 subjects included in analysis, 177 reported sleep apnea. Age-standardized and design-effect-corrected prevalence rates were differential across gender, plasma homocysteine, and red cell folate status. Plasma homocysteine was positively correlated with age (r = 0.38, P < 0.0001). Multivariate analyses using sociodemographic and clinical covariates demonstrated that plasma homocysteine levels retained their respective associations with self-reported sleep apnea in all models except when age was included as a covariate. Our results demonstrate that the claimed association of plasma homocysteine with sleep apnea may be confounded by age.