Corneal nerve loss is related to the severity of painful diabetic neuropathy.

BACKGROUND AND PURPOSE: Previously it has been shown that patients with painful diabetic neuropathy (PDN) have greater corneal nerve loss compared to patients with painless diabetic neuropathy. This study investigated if the severity of corneal nerve loss was related to the severity of PDN. METHODS: Participants with diabetic neuropathy (n = 118) and healthy controls (n = 38) underwent clinical and neurological evaluation, quantitative sensory testing, nerve conduction testing and corneal confocal microscopy and were categorized into those with no (n = 43), mild (n = 34) and moderate-to-severe (n = 41) neuropathic pain. RESULTS: Corneal nerve fibre density (p = 0.003), corneal nerve fibre length (p < 0.0001) and cold perception threshold (p < 0.0001) were lower and warm perception threshold was higher (p = 0.002) in patients with more severe pain, but there was no significant difference in the neuropathy disability score (p = 0.5), vibration perception threshold (p = 0.5), sural nerve conduction velocity (p = 0.3) and amplitude (p = 0.7), corneal nerve branch density (p = 0.06) and deep breathing heart rate variability (p = 0.08) between patients with differing severity of PDN. The visual analogue scale correlated significantly with corneal nerve fibre density (r = -0.3, p = 0.0002), corneal nerve branch density (r = -0.3, p = 0.001) and corneal nerve fibre length (r = -0.4, p < 0.0001). Receiver operating curve analysis showed that corneal nerve fibre density had an area under the curve of 0.78 with a sensitivity of 0.73 and specificity of 0.72 for the diagnosis of PDN. CONCLUSIONS: Corneal confocal microscopy reveals increasing corneal nerve fibre loss with increasing severity of neuropathic pain and a good diagnostic outcome for identifying patients with PDN.

Optimal Utility of H-Reflex RDD as a Biomarker of Spinal Disinhibition in Painful and Painless Diabetic Neuropathy.

Impaired rate-dependent depression of the Hoffman reflex (HRDD) is a potential biomarker of impaired spinal inhibition in patients with painful diabetic neuropathy. However, the optimum stimulus-response parameters that identify patients with spinal disinhibition are currently unknown. We systematically compared HRDD, performed using trains of 10 stimuli at five stimulation frequencies (0.3, 0.5, 1, 2 and 3 Hz), in 42 subjects with painful and 62 subjects with painless diabetic neuropathy with comparable neuropathy severity, and 34 healthy controls. HRDD was calculated using individual and mean responses compared to the initial response. At stimulation frequencies of 1, 2 and 3 Hz, HRDD was significantly impaired in patients with painful diabetic neuropathy compared to patients with painless diabetic neuropathy for all parameters and for most parameters when compared to healthy controls. HRDD was significantly enhanced in patients with painless diabetic neuropathy compared to controls for responses towards the end of the 1 Hz stimulation train. Receiver operating characteristic curve analysis in patients with and without pain showed that the area under the curve was greatest for response averages of stimuli 2-4 and 2-5 at 1 Hz, AUC = 0.84 (95%CI 0.76-0.92). Trains of 5 stimuli delivered at 1 Hz can segregate patients with painful diabetic neuropathy and spinal disinhibition, whereas longer stimulus trains are required to segregate patients with painless diabetic neuropathy and enhanced spinal inhibition.

Spinal Inhibitory Dysfunction in Patients With Painful or Painless Diabetic Neuropathy.

OBJECTIVE: Impaired rate-dependent depression of the Hoffman reflex (HRDD) is a marker of spinal inhibitory dysfunction and has previously been associated with painful neuropathy in a proof-of-concept study in patients with type 1 diabetes. We have now undertaken an assessment of HRDD in patients with type 1 or type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 148 participants, including 34 healthy control subjects, 42 patients with painful diabetic neuropathy, and 62 patients with diabetic neuropathy without pain, underwent an assessment of HRDD and a detailed assessment of peripheral neuropathy, including nerve conduction studies, corneal confocal microscopy, and thermal threshold testing. RESULTS: Compared with healthy control subjects (P < 0.001) and patients without pain (P < 0.001), we found that HRDD is impaired in patients with type 1 or type 2 diabetes with neuropathic pain. These impairments are unrelated to diabetes type and the presence or severity of neuropathy. In contrast, patients without neuropathic pain (P < 0.05) exhibited enhanced HRDD compared with control subjects. CONCLUSIONS: We suggest that loss or impairment of HRDD may help to identify a subpopulation of patients with painful diabetic neuropathy mediated by impaired spinal inhibitory systems who may respond optimally to therapies that target spinal or supraspinal mechanisms. Enhanced RDD in patients without pain may reflect engagement of spinal pain-suppressing mechanisms.

Corneal confocal microscopy compared with quantitative sensory testing and nerve conduction for diagnosing and stratifying the severity of diabetic peripheral neuropathy.

INTRODUCTION: Diabetic neuropathy can be diagnosed and assessed using a number of techniques including corneal confocal microscopy (CCM). RESEARCH DESIGN AND METHODS: We have undertaken quantitative sensory testing, nerve conduction studies and CCM in 143 patients with type 1 and type 2 diabetes without neuropathy (n=51), mild neuropathy (n=47) and moderate to severe neuropathy (n=45) and age-matched controls (n=30). RESULTS: Vibration perception threshold (p<0.0001), warm perception threshold (WPT) (p<0.001), sural nerve conduction velocity (SNCV) (p<0.001), corneal nerve fiber density (CNFD) (p<0.0001), corneal nerve branch density (CNBD) (p<0.0001), corneal nerve fiber length (CNFL) (p=0.002), inferior whorl length (IWL) (p=0.0001) and average nerve fiber length (ANFL) (p=0.0001) showed a progressive abnormality with increasing severity of diabetic neuropathy. Receiver operating characteristic curve analysis for the diagnosis of diabetic neuropathy showed comparable performance in relation to the area under the curve (AUC) but differing sensitivities and specificities for vibration perception threshold (AUC 0.79, sensitivity 55%, specificity 90%), WPT (AUC 0.67, sensitivity 50%, specificity 76%), cold perception threshold (AUC 0.64, sensitivity 80%, specificity 47%), SNCV (AUC 0.70, sensitivity 76%, specificity 54%), CNFD (AUC 0.71, sensitivity 58%, specificity 83%), CNBD (AUC 0.70, sensitivity 69%, specificity 65%), CNFL (AUC 0.68, sensitivity 64%, specificity 67%), IWL (AUC 0.72, sensitivity 70%, specificity 65%) and ANFL (AUC 0.72, sensitivity 71%, specificity 66%). CONCLUSION: This study shows that CCM identifies early and progressive corneal nerve loss at the inferior whorl and central cornea and has comparable utility with quantitative sensory testing and nerve conduction in the diagnosis of diabetic neuropathy.

Integrated virtual and cadaveric dissection laboratories enhance first year medical students' anatomy experience: a pilot study.

BACKGROUND: Radiology integration into medical anatomy courses is well established, but there is a paucity of literature on integrating virtual dissection into cadaveric dissection laboratories. Virtual dissection is the digital dissection of medical images on touchscreen anatomy visualization tables. The purpose of this pilot study was to investigate the feasibility of integrating virtual dissection into a first-year medical cadaver-based anatomy course and to assess students' overall attitude towards this new technology. METHODS: All students in first-year medicine at a single medical school participated in this study (n = 292). Six virtual dissection laboratories, which focused on normal anatomy, were developed and integrated into a cadaver-based anatomy course. The virtual dissection table (VDT) was also integrated into the final anatomy spot exam. Following the course, students completed a short evidence-informed survey which was developed using a theoretical framework for curriculum evaluation. Numerical data were tabulated, and qualitative content analysis was performed on students' unstructured comments. RESULTS: The survey response rate was 69.2% (n = 202/292). Most (78.7%) students reported that virtual dissection enhanced their understanding of the cadaveric anatomy and the clinical applications of anatomy. Most (73.8%) students also felt that the VDT was an effective use of the laboratory time. Thirteen narrative comments were collected, most of which (61.5%) identified strengths of the curriculum. CONCLUSIONS: In this pilot study, students perceived that their learning was enhanced when virtual dissection was combined with a cadaver-based anatomy laboratory. This study demonstrates that there is potential for virtual dissection to augment cadaveric dissection in medical education.

Implementation of a Longitudinal Introduction to Radiology Course During Internship Year Improves Diagnostic Radiology Residents' Academic and Clinical Skills: A Canadian Experience.

RATIONALE AND OBJECTIVES: In order to ease the transition from internship to diagnostic radiology residency, a year-long didactic introduction to radiology course was offered to post-graduate year one (PGY-1) diagnostic radiology residents during their internship, which consisted of 27 hours of lecture over 9 months. The purpose of this study was to determine the quantitative and qualitative educational value of this course and its effect with respect to on-call preparedness. MATERIALS AND METHODS: Two consecutive cohorts of Diagnostic Radiology residents were included: the first cohort (PGY-1s in 2011-2012) did not participate in the new course (Old Curriculum Residents) and the second cohort (PGY-1s in 2012-2013) completed the new course (New Curriculum Residents). These two cohorts were compared both qualitatively and quantitatively. Scores were compared from the standardized Canadian National Pre-Call Observed Standardized Clinical Examination and American College of Radiology Diagnostic Radiology In-Training examination, which are taken in the PGY-2 year, at months 5 and 7, respectively. In addition, staff observation of on-call resident performance and resident self-reported preparedness were considered. Cohorts were compared using Mann-Whitney U test with significance defined as P value <0.05. P values from 0.05 to 0.10 were noted as possibly significant and further analyzed using a Cohen d test where the difference was determined to be small (0.2), medium (0.5), or large (0.8). RESULTS: New Curriculum Residents reported that the content of the PGY1 curriculum was more appropriate than the old curriculum to prepare them for call in PGY2 (P = 0.013). New Curriculum Residents scored better than the Old Curriculum Residents on the Diagnostic Radiology In-Training examination (P = 0.039) and on the emergency cases of the Canadian National Pre-Call Observed Standardized Clinical Examination (P = 0.035). Staff radiologists, who were not blinded, reported that the New Curriculum Residents were better prepared for daytime (P = 0.006) and overnight (P = 0.008) independent call were better prepared to perform common ultrasound examinations alone (P = 0.049), and required less guidance while on call for nine competency areas. There was, however, no statistical difference between the residents' self-reported preparedness for independent call. CONCLUSIONS: Participation in a lecture-based introductory radiology curriculum during the PGY-1 internship year improved both radiology residents' preparedness for call and their performance in PGY-2.

Unintentional injury mortality among American Indians and Alaska Natives in the United States, 1990-2009.

OBJECTIVES: We describe the burden of unintentional injury (UI) deaths among American Indian and Alaska Native (AI/AN) populations in the United States. METHODS: National Death Index records for 1990 to 2009 were linked with Indian Health Service registration records to identify AI/AN deaths misclassified as non-AI/AN deaths. Most analyses were restricted to Contract Health Service Delivery Area counties in 6 geographic regions of the United States. We compared age-adjusted death rates for AI/AN persons with those for Whites; Hispanics were excluded. RESULTS: From 2005 to 2009, the UI death rate for AI/AN people was 2.4 times higher than for Whites. Death rates for the 3 leading causes of UI death-motor vehicle traffic crashes, poisoning, and falls-were 1.4 to 3 times higher among AI/AN persons than among Whites. UI death rates were higher among AI/AN males than among females and highest among AI/AN persons in Alaska, the Northern Plains, and the Southwest. CONCLUSIONS: AI/AN persons had consistently higher UI death rates than did Whites. This disparity in overall rates coupled with recent increases in unintentional poisoning deaths requires that injury prevention be a major priority for improving health and preventing death among AI/AN populations.