Concurrent validity ROC curves for sural, peroneal, tibial and summative parameters.

<p>See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0058783#pone-0058783-t002" target="_blank">Table 2</a> for estimates of AROC for each parameter. Peroneal conduction velocity and sural amplitude potential had the highest AROC (AROC 0.90 and 0.83, respectively). Dashed lines represent amplitude potentials. Solid lines represent conduction velocities. Dotted lines represent F-wave latencies.</p

Comparison of Area Under the Receiver Operating Characteristic Curve (AROC) Between Individual and Summative NCS Parameters for the Cross-Cectional (Concurrent Validity) Analysis and the Longitudinal (Predictive Validity) Analysis.

<p>Normal values for individual NCS are as follows. Sural amp≥7.2 µV for age ≤65 and ≥5.5 µV for age >65, sural CV≥40 m/s, peroneal amp≥5 µV for age ≤65 and ≥3 for age >65, peroneal CV≥40 m/s, peroneal F wave ≤59 ms for height ≥182.9 cm and ≤58 ms for height ≤182.9 cm, tibial amp≥10 µV, tibial CV≥40 m/s, tibial F wave ≤55 ms.</p>*<p>Two tailed p value for comparison with the AROC for the parameters with the highest AROC in concurrent and predictive analyses.</p>†<p>Established by the distribution in healthy control subects <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0058783#pone.0058783-Oh1" target="_blank">[23]</a>.</p>‡<p>Summative parameters are composed of the following: sum amplitude = sural+tibial, sum conduction velocity = sural+peroneal +tibial, sum F-wave latency = peroneal+tibial. Summed amplitude potentials are expressed in arbitrary units since sural amplitude potential is measured in microvolts and tibial amplitude potential is measured in millivolts.</p><p> <b>Amp, amplitude potential. CV, conduction velocity. F-wave, F-wave latency.</b></p

Predictive validity ROC curves for sural, peroneal, tibial and summative parameters.

<p>See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0058783#pone-0058783-t002" target="_blank">Table 2</a> for estimates of AROC for each parameter. Tibial F-wave latency and the sum of sural, peroneal, and tibial conduction velocities had the highest AROC (0.80 and 0.83, respectively). Dashed lines represent amplitude potentials. Solid lines represent conduction velocities. Dotted lines represent F-wave latencies.</p

Baseline Characteristics of the 251 Prevalent DSP Cases and the 107 Prevalent Controls According to the 4-Year Incidence of DSP.

<p>Data are means ± standard deviations or <i>n</i> (%). For comparisons between two groups, p values reported are χ² test statistics for categorical variables and T-tests for continuous variables. For comparisons between three groups, p values reported are χ² test statistics for categorical variables and ANOVA for continuous variables. Normal values for individual NCS are as follows. Sural amp≥7.2 µV for age ≤65 and ≥5.5 µV for age >65, sural CV≥40 m/s, peroneal amp≥5 µV for age ≤65 and ≥3 for age >65, peroneal CV≥40 m/s, peroneal F wave ≤59 ms for height ≥182.9 cm and ≤58 ms for height ≤182.9 cm, tibial amp≥10 µV, tibial CV≥40 m/s, tibial F wave ≤55 ms.</p>*<p>p-value for ANOVA between Prevalent Cases, Incident DSP Cases and Incident DSP Controls.</p>†<p>By subject self-report.</p>‡<p>HbA1C, glycated hemoglobin A1C.</p>§<p>Summative parameters are composed of the following: sum amplitude = sural+tibial, sum conduction velocity = sural+peroneal +tibial, sum F-wave latency = peroneal+tibial.</p>¶<p>Summed amplitude potentials are expressed in arbitrary units since sural amplitude potential is measured in microvolts and tibial amplitude potential is measured in millivolts.</p>∥<p>Statistical tests for the NCS parameters applied a Bonferroni correction for multiple comparisons for significance such that p-values <0.0045 (0.05/11) were considered significant. All p-values except for two indicated by this symbol, met significance criteria.</p><p> <b>TCNS, Toronto Clinical Neuropathy Score. Amp, amplitude potential. CV, conduction velocity. F-wave, F-wave latency.</b></p

Distribution of CDT values according to DSP case-control status in the 52 healthy volunteers and 136 subjects with type 1 diabetes.

<p>Horizontal bars represent the median for each group.</p

Characteristics of 52 healthy volunteers and 136 subjects with type 1 diabetes.

<p>Data presented as mean ± sd and/or median[IQR], unless otherwise noted. P-values for comparison are from the ANOVA test (for continuous parametric variables), the Kruskal-Wallis test (for continuous non-parametric variables), or from logistic regression (for dichotomous variables).</p><p>DSP, diabetic sensory polyneuropathy; TCNS, Toronto clinical neuropathy score; HbA1c, glycated hemoglobin; LDL, low density lipoprotein; ACR, albumin-to-creatinine ratio from spot urine samples; eGFR, estimated glomerular filtration rate; LDI_FLARE, axon–reflex mediated neurogenic vasodilatation in response to cutaneous heating by the laser doppler imaging flare technique.</p><p>Characteristics of 52 healthy volunteers and 136 subjects with type 1 diabetes.</p

ROC curves for functional small fiber measures and the TCNS in the identification of clinical DSP in 136 Subjects with type 1 diabetes.

<p>Clinical DSP was defined as having a nerve conduction abnormality in both the sural sensory nerve and peroneal motor nerve, in addition to at least one clinical sign or symptom. AUCs for CDT, TCNS, HRV, and LDI were 0.863, 0.858, 0.788, and 0.745, respectively. The optimal threshold for CDT (*) was 25.1°C (83% sensitivity, 82% specificity).</p

Reproducibility of <i>In Vivo</i> Corneal Confocal Microscopy Using an Automated Analysis Program for Detection of Diabetic Sensorimotor Polyneuropathy

<div><p>Objective</p><p><i>In vivo</i> Corneal Confocal Microscopy (IVCCM) is a validated, non-invasive test for diabetic sensorimotor polyneuropathy (DSP) detection, but its utility is limited by the image analysis time and expertise required. We aimed to determine the inter- and intra-observer reproducibility of a novel automated analysis program compared to manual analysis.</p><p>Methods</p><p>In a cross-sectional diagnostic study, 20 non-diabetes controls (mean age 41.4±17.3y, HbA1c 5.5±0.4%) and 26 participants with type 1 diabetes (42.8±16.9y, 8.0±1.9%) underwent two separate IVCCM examinations by one observer and a third by an independent observer. Along with nerve density and branch density, corneal nerve fibre length (CNFL) was obtained by manual analysis (CNFL_MANUAL), a protocol in which images were manually selected for automated analysis (CNFL_{SEMI-AUTOMATED}), and one in which selection and analysis were performed electronically (CNFL_{FULLY-AUTOMATED}). Reproducibility of each protocol was determined using intraclass correlation coefficients (ICC) and, as a secondary objective, the method of Bland and Altman was used to explore agreement between protocols.</p><p>Results</p><p>Mean CNFL_Manual was 16.7±4.0, 13.9±4.2 mm/mm² for non-diabetes controls and diabetes participants, while CNFL_{Semi-Automated} was 10.2±3.3, 8.6±3.0 mm/mm² and CNFL_{Fully-Automated} was 12.5±2.8, 10.9 ± 2.9 mm/mm². Inter-observer ICC and 95% confidence intervals (95%CI) were 0.73(0.56, 0.84), 0.75(0.59, 0.85), and 0.78(0.63, 0.87), respectively (p = NS for all comparisons). Intra-observer ICC and 95%CI were 0.72(0.55, 0.83), 0.74(0.57, 0.85), and 0.84(0.73, 0.91), respectively (p<0.05 for CNFL_{Fully-Automated} compared to others). The other IVCCM parameters had substantially lower ICC compared to those for CNFL. CNFL_{Semi-Automated} and CNFL_{Fully-Automated} underestimated CNFL_Manual by mean and 95%CI of 35.1(-4.5, 67.5)% and 21.0(-21.6, 46.1)%, respectively.</p><p>Conclusions</p><p>Despite an apparent measurement (underestimation) bias in comparison to the manual strategy of image analysis, fully-automated analysis preserves CNFL reproducibility. Future work must determine the diagnostic thresholds specific to the fully-automated measure of CNFL.</p></div

Agreement between CNFL_Manual and CNFL_{Semi-Automated}.

<p>In Panels A and B, the reference lines, from top to bottom, denote the 97.5th percentile, the mean, and the 2.5th percentile for the indicated differences.</p

Intra Class Correlation coefficients for all non-diabetes controls (n = 20).

<p>ICC: Intra-class correlation coefficient (2, 1). Inter refers to inter-observer reproducibility, intra to intra-observer reproducibility. The manual protocol included manual image selection and manual image analysis. The semi-automated protocol included manual image selection and automated analysis. The fully-automated protocol included automated image selection and automated analysis. CNFL, corneal nerve fibre length. CNFD, corneal nerve fibre density. CNBD, corneal nerve branch density.</p><p>* Manual protocol ICC have been presented in a previous publication and are shown here for comparison.</p><p>Intra Class Correlation coefficients for all non-diabetes controls (n = 20).</p