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1.
Comput Biol Med ; 122: 103814, 2020 07.
Article in English | MEDLINE | ID: mdl-32658728

ABSTRACT

BACKGROUND: Studies which use external tocography to explore the relationship between increased intrapartum uterine activity and foetal outcomes are feasible because the technology is safe and ubiquitous. However, periods of poor signal quality are common. We developed an algorithm which aims to calculate tocograph summary variables based on well-recorded contractions only, ignoring artefact and excluding sections deemed uninterpretable. The aim of this study was to test that algorithm's reliability. METHODS: Whole recordings from labours at ≥35 weeks of gestation were randomly selected without regard to quality. Contractions and rest intervals were measured by two humans independently, and by the algorithm using two sets of models; one based on a series of pre-defined thresholds, and another trained to imitate one of the human interpreters. The absolute agreement intraclass correlation coefficient (ICC) was calculated using a two-way random effects model. RESULTS: The training dataset included data from 106 tocographs. Of the tested algorithms, AdaBoost showed the highest initial cross-validated accuracy and proceeded to optimization. Forty tocographs were included in the validation set. The ICCs for the per tocograph mean contraction rates were; human B to human A: 0.940 (0.890-0.968), human A to initial models: 0.944 (0.898-0.970), human A to trained models 0.962 (0.927-0.980), human B to initial models: 0.930 (0.872-0.962), human B to trained models: 0.948 (0.903-0.972). CONCLUSIONS: The algorithm described approximates interpretation of external tocography performed by trained humans. The performance of the AdaBoost trained models was marginally superior compared to the initial models.


Subject(s)
Labor, Obstetric , Uterine Monitoring , Adolescent , Algorithms , Female , Humans , Pregnancy , Reproducibility of Results , Uterine Contraction
2.
Diabetes Care ; 43(8): 1829-1835, 2020 08.
Article in English | MEDLINE | ID: mdl-32139385

ABSTRACT

OBJECTIVE: Corneal nerve fiber length (CNFL) represents a biomarker for diabetic distal symmetric polyneuropathy (DSP). We aimed to determine the reference distribution of annual CNFL change, the prevalence of abnormal change in diabetes, and its associated clinical variables. RESEARCH DESIGN AND METHODS: We examined 590 participants with diabetes (399 with type 1 diabetes [T1D] and 191 with type 2 diabetes [T2D]) and 204 control patients without diabetes with at least 1 year of follow-up and classified them according to rapid corneal nerve fiber loss (RCNFL) if CNFL change was below the 5th percentile of the control patients without diabetes. RESULTS: Control patients without diabetes were 37.9 ± 19.8 years old, had median follow-up of three visits over 3.0 years, and mean annual change in CNFL was -0.1% (90% CI -5.9% to 5.0%). RCNFL was defined by values exceeding the 5th percentile of 6% loss. Participants with T1D were 39.9 ± 18.7 years old, had median follow-up of three visits over 4.4 years, and mean annual change in CNFL was -0.8% (90% CI -14.0% to 9.9%). Participants with T2D were 60.4 ± 8.2 years old, had median follow-up of three visits over 5.3 years, and mean annual change in CNFL was -0.2% (90% CI -14.1% to 14.3%). RCNFL prevalence was 17% overall and was similar by diabetes type (64 T1D [16.0%], 37 T2D [19.4%], P = 0.31). RNCFL was more common in those with baseline DSP (47% vs. 30% in those without baseline DSP, P = 0.001), which was associated with lower peroneal conduction velocity but not with baseline HbA1c or its change over follow-up. CONCLUSIONS: An abnormally rapid loss of CNFL of 6% per year or more occurs in 17% of diabetes patients. RCNFL may identify patients at highest risk for the development and progression of DSP.


Subject(s)
Cornea/innervation , Diabetes Mellitus, Type 1/diagnosis , Diabetes Mellitus, Type 2/diagnosis , Diabetic Neuropathies/diagnosis , Nerve Fibers/pathology , Adolescent , Adult , Aged , Biomarkers/analysis , Case-Control Studies , Cell Count , Cornea/diagnostic imaging , Cornea/pathology , Corneal Diseases/diagnosis , Corneal Diseases/etiology , Corneal Diseases/pathology , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 1/pathology , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/pathology , Diabetic Neuropathies/pathology , Diabetic Neuropathies/physiopathology , Disease Progression , Female , Follow-Up Studies , Humans , Male , Microscopy, Confocal , Middle Aged , Prognosis , Time Factors , Young Adult
3.
J Diabetes Complications ; 31(8): 1318-1324, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28599823

ABSTRACT

AIM: To determine the association of neuropathy and other complications with emotional distress and depression among patients with longstanding type 1 diabetes (T1DM). METHODS: Canadians with ≥50years of T1DM completed a questionnaire including assessment of distress and depression by the Problem Areas in Diabetes Scale (PAID) and Geriatric Depression Scale (GDS), respectively. Complications were determined using the Michigan Neuropathy Screening Instrument (Questionnaire Component), fundoscopy reports, renal function tests, and self-reported peripheral-(PVD) and cardiovascular (CVD) disease. Associations were analyzed by Poisson regression. RESULTS: Among 323 participants, 137 (42.4%) had neuropathy, 113 (36.5%) nephropathy, 207 (69.5%) retinopathy, 95 (29.4%) CVD, and 31 (9.8%) PVD. The neuropathy subgroup had higher prevalence of distress (13 (9.5%) vs. 6 (3.3%), p=0.029) and depression (34 (24.9%) vs. 12 (6.5%), p<0.001). Adjusting for diabetes complications, neuropathy was associated with higher PAID (adjusted RR 1.44 (95% CI 1.14-1.82), p=0.003) and GDS scores (adjusted RR1.57 (1.18-2.11), p=0.002). Independent of potential confounders, neuropathy remained associated with higher PAID (adjusted RR 1.39 (1.10-1.76), p=0.006) and GDS scores (adjusted RR 1.37 (1.03-1.83), p=0.032). Associations with neuropathy were not fully explained by neuropathic pain. CONCLUSION: Compared to other complications, neuropathy had the greatest association with distress and depression in longstanding T1DM, independent of pain. Strategies beyond pain management are needed to improve quality of life in diabetic neuropathy.


Subject(s)
Aging , Cost of Illness , Depressive Disorder, Major/complications , Diabetes Mellitus, Type 1/complications , Diabetic Neuropathies/complications , Quality of Life , Stress, Physiological , Aged , Aged, 80 and over , Canada/epidemiology , Cohort Studies , Cross-Sectional Studies , Depressive Disorder, Major/epidemiology , Depressive Disorder, Major/mortality , Depressive Disorder, Major/psychology , Diabetes Mellitus, Type 1/mortality , Diabetes Mellitus, Type 1/psychology , Diabetic Neuropathies/mortality , Diabetic Neuropathies/psychology , Female , Humans , Longevity , Male , Middle Aged , Poisson Distribution , Prevalence , Psychiatric Status Rating Scales , Risk , Survival Analysis
4.
J Diabetes Complications ; 31(6): 1066-1073, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28347694

ABSTRACT

AIMS: Quantification of corneal nerve fiber length (CNFL) by in vivo corneal confocal microscopy represents a promising diabetic neuropathy biomarker, but applicability is limited by resource-intensive image analysis. We aimed to evaluate, in cross-sectional analysis of non-diabetic controls and patients with type 1 and type 2 diabetes with and without neuropathy, the agreement between manual and automated analysis protocols. METHODS: Sixty-eight controls, 139 type 1 diabetes, and 249 type 2 diabetes participants underwent CNFL measurement (N=456). Neuropathy status was determined by clinical and electrophysiological criteria. CNFL was determined by manual (CNFLManual, reference standard) and automated (CNFLAuto) protocols, and results were compared for correlation and agreement using Spearman coefficients and the method of Bland and Altman (CNFLManual subtracted from CNFLAuto). RESULTS: Participants demonstrated broad variability in clinical characteristics associated with neuropathy. The mean age, diabetes duration, and HbA1c were 53±18years, 15.9±12.6years, and 7.4±1.7%, respectively, and 218 (56%) individuals with diabetes had neuropathy. Mean CNFLManual was 15.1±4.9mm/mm2, and mean CNFLAuto was 10.5±3.7mm/mm2 (CNFLAuto underestimation bias, -4.6±2.6mm/mm2 corresponding to -29±17%). Percent bias was similar across non-diabetic controls (-33±12%), type 1 (-30±20%), and type 2 diabetes (-28±16%) subgroups (ANOVA, p=0.068), and similarly in diabetes participants with and without neuropathy. Levels of CNFLAuto and CNFLManual were both inversely associated with neuropathy status. CONCLUSIONS: Although CNFLAuto substantially underestimated CNFLManual, its bias was non-differential between diverse patient groups and its relationship with neuropathy status was preserved. Determination of diagnostic thresholds specific to CNFLAuto should be pursued in diagnostic studies of diabetic neuropathy.


Subject(s)
Cornea/innervation , Cornea/pathology , Diabetic Neuropathies/diagnosis , Diagnostic Techniques, Ophthalmological , Image Processing, Computer-Assisted/methods , Nerve Fibers/pathology , Adult , Aged , Case-Control Studies , Cross-Sectional Studies , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 1/diagnosis , Diabetes Mellitus, Type 1/pathology , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/pathology , Diabetic Neuropathies/pathology , Diabetic Retinopathy/diagnosis , Diabetic Retinopathy/pathology , Female , Humans , Male , Microscopy, Confocal , Middle Aged , Pattern Recognition, Automated/methods , Physical Examination/methods
5.
Diabetes Technol Ther ; 18(5): 298-307, 2016 05.
Article in English | MEDLINE | ID: mdl-27023749

ABSTRACT

OBJECTIVE: We aimed to determine cross-sectional insulin pump prevalence and factors associated with measures of glycemic control as a secondary analysis in a long-standing type 1 diabetes mellitus (T1DM) national cohort. RESEARCH DESIGN AND METHODS: Canadian participants with ≥50 years of T1DM (n = 305) were administered a comprehensive mail-based questionnaire including acquisition of contemporaneous laboratory results. Factors associated with pump use, glycosylated hemoglobin (HbA1c), and hypoglycemia were analyzed by regression. RESULTS: The 305 participants had a median age of 65 [interquartile range, 59, 71] years, median diabetes duration of 54 [51, 59] years, and mean HbA1c level of 7.5 ± 1.1%. Prevalence of pump use was 44% (133/305), with median duration of use 8 [4, 13] years. Compared with the non-pump subgroup, the pump subgroup had numerically lower but similar HbA1c levels (7.4 ± 0.9% vs. 7.6 ± 1.2%; P = 0.22) and reported greater numbers of minor hypoglycemia events (6.5 vs. 5.1 events/patient·month; P = 0.004) and fewer severe hypoglycemia events (0.5 vs. 1.3 events/patient·year; P = 0.02) in the past year. More frequent daily glucose tests and more frequent minor hypoglycemia events-but not pump therapy or its prescription parameters-were independently associated with lower HbA1c level in multivariable regression. However, use of insulin pump and habitual use of continuous glucose monitoring (≥1 week/month) were each independently associated with lower risk of severe hypoglycemia (risk ratio = 0.50 [P < 0.0001] and 0.30 [P = 0.001], respectively). CONCLUSIONS: Insulin pump and continuous glucose monitoring technologies were associated with lower risk of severe hypoglycemia, while frequent daily glucose testing was associated with lower HbA1c level. These findings imply that basic self-management skill and technology play complementary roles in glycemic control among older adults with long-standing T1DM.


Subject(s)
Diabetes Mellitus, Type 1/drug therapy , Hypoglycemic Agents/administration & dosage , Insulin Infusion Systems/statistics & numerical data , Insulin/administration & dosage , Aged , Cohort Studies , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Treatment Outcome
7.
J Diabetes Complications ; 30(4): 716-22, 2016.
Article in English | MEDLINE | ID: mdl-26994558

ABSTRACT

AIM: We aimed to validate the performance cooling detection thresholds (CDT) to detect diabetic sensorimotor polyneuropathy (DSP) in type 2 diabetes. METHODS: Two hundred and twenty participants with type 2 diabetes underwent clinical and electrophysiological examinations including 3 small fiber function tests: CDT, heart rate variability (HRV) and LDIFLARE. Clinical DSP was defined by consensus criteria whereas preclinical DSP was defined by presence of at least one electrophysiological abnormality. Area under the curve (AUC) and optimal thresholds were determined by receiver operating characteristic curves. RESULTS: Participants were aged 63 ± 11 years with mean HbA1c of 7.5 ± 1.6%. The 139 (63%) clinical DSP cases had mean CDT values of 18.3 ± 8.9°C; the 52 (24%) preclinical DSP cases had 25.3 ± 3.5°C; and the 29 (13%) controls had 27.1 ± 3.8°C; (p-value<0.02 for all comparisons). For identification of clinical DSP cases, AUCCDT was 0.79 which exceeded AUCHRV (0.60, p=<0.0001) and AUCLDI FLARE (0.69, p=0.0003), optimal threshold <22.8°C (64% sensitivity, 83% specificity). Preclinical DSP AUCCDT was 0.80, also exceeding the other 2 measures (p<0.02 for both comparisons), optimal threshold ≤27.5°C (83% sensitivity, 72% specificity). CONCLUSIONS: CDT had good diagnostic performance for identification of both clinical and preclinical neuropathy in type 2 diabetes. Its use as a non-invasive screening tool should be considered for research and clinical practice.


Subject(s)
Asymptomatic Diseases , Diabetes Mellitus, Type 2/complications , Diabetic Neuropathies/diagnosis , Polyneuropathies/diagnosis , Aged , Biomarkers , Cohort Studies , Cold Temperature , Cross-Sectional Studies , Diabetes Mellitus, Type 2/blood , Early Diagnosis , Glycated Hemoglobin/analysis , Hospitals, General , Hospitals, Urban , Humans , Middle Aged , Ontario , Outpatient Clinics, Hospital , Polyneuropathies/complications , Predictive Value of Tests , Sensitivity and Specificity , Sensory Thresholds
8.
Cardiovasc Diabetol ; 15: 14, 2016 Jan 25.
Article in English | MEDLINE | ID: mdl-26809442

ABSTRACT

BACKGROUND: Older patients with longstanding type 1 diabetes have high cardiovascular disease (CVD) risk such that statin therapy is recommended independent of prior CVD events. We aimed to determine self-reported CVD prevention guideline adherence in patients with longstanding diabetes. RESEARCH DESIGN AND METHODS: 309 Canadians with over 50 years of type 1 diabetes completed a medical questionnaire for presence of lifestyle and pharmacological interventions, stratified into primary or secondary CVD prevention subgroups based on absence or presence of self-reported CVD events, respectively. Associations with statin use were analyzed using multivariable logistic regression. RESULTS: The 309 participants had mean ± SD age 65.7 ± 8.5 years, median diabetes duration 54.0 [IQR 51.0, 59.0] years, and HbA1c of 7.5 ± 1.1 % (58 mmol/mol). 159 (52.7 %) participants reported diet adherence, 296 (95.8 %) smoking avoidance, 217 (70.5 %) physical activity, 218 (71.5 %) renin-angiotensin-system inhibitor use, and 220 (72.1 %) statin use. Physical activity was reported as less common in the secondary prevention subgroup, and current statin use was significantly lower in the primary prevention subgroup (65.5 % vs. 84.8 %, p = 0.0004). In multivariable logistic regression, the odds of statin use was 0.38 [95 % CI 0.15-0.95] in members of the primary compared to the secondary prevention subgroup, adjusting for age, sex, hypertension history, body mass, HbA1c, cholesterol, microvascular complications, acetylsalicylic acid use, and renin-angiotensin system inhibitor use. CONCLUSION: Despite good self-reported adherence to general CVD prevention guidelines, against the principles of these guidelines we found that statin use was substantially lower in those without CVD history. Interventions are needed to improve statin use in older type 1 diabetes patients without a history of CVD.


Subject(s)
Cardiovascular Diseases/prevention & control , Diabetes Mellitus, Type 1/therapy , Dyslipidemias/drug therapy , Guideline Adherence , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Longevity , Medication Adherence , Primary Prevention/methods , Risk Reduction Behavior , Secondary Prevention/methods , Aged , Angiotensin II Type 1 Receptor Blockers/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Canada , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/epidemiology , Chi-Square Distribution , Cross-Sectional Studies , Diabetes Mellitus, Type 1/diagnosis , Diabetes Mellitus, Type 1/epidemiology , Diet/adverse effects , Dyslipidemias/diagnosis , Dyslipidemias/epidemiology , Exercise , Female , Health Care Surveys , Humans , Logistic Models , Male , Middle Aged , Motor Activity , Multivariate Analysis , Odds Ratio , Practice Guidelines as Topic , Risk Factors , Self Report , Smoking/adverse effects , Smoking Cessation , Smoking Prevention , Time Factors , Treatment Outcome
9.
PLoS One ; 10(11): e0142309, 2015.
Article in English | MEDLINE | ID: mdl-26539984

ABSTRACT

OBJECTIVE: In vivo 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. METHODS: 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 (CNFLMANUAL), a protocol in which images were manually selected for automated analysis (CNFLSEMI-AUTOMATED), and one in which selection and analysis were performed electronically (CNFLFULLY-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. RESULTS: Mean CNFLManual was 16.7±4.0, 13.9±4.2 mm/mm2 for non-diabetes controls and diabetes participants, while CNFLSemi-Automated was 10.2±3.3, 8.6±3.0 mm/mm2 and CNFLFully-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 CNFLFully-Automated compared to others). The other IVCCM parameters had substantially lower ICC compared to those for CNFL. CNFLSemi-Automated and CNFLFully-Automated underestimated CNFLManual by mean and 95%CI of 35.1(-4.5, 67.5)% and 21.0(-21.6, 46.1)%, respectively. CONCLUSIONS: 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.


Subject(s)
Cornea/pathology , Diabetes Mellitus, Type 1/complications , Diabetic Neuropathies/etiology , Diabetic Neuropathies/pathology , Polyneuropathies/etiology , Polyneuropathies/pathology , Adult , Cross-Sectional Studies , Female , Humans , Male , Microscopy, Confocal/methods , Middle Aged , Reproducibility of Results
10.
Can J Diabetes ; 39(5): 390-7, 2015 Oct.
Article in English | MEDLINE | ID: mdl-25936902

ABSTRACT

OBJECTIVE: In vivo corneal confocal microscopy (IVCCM) has been established in cross-sectional studies as a valid measure for the identification of diabetic sensorimotor polyneuropathy (DSP). We aimed to determine the predictive validity of a baseline IVCCM measure in identifying future DSP onset in patients with type 1 diabetes. METHODS: We followed 65 patients with type 1 diabetes without DSP at baseline. They were followed longitudinally for a mean of 3.5±0.9 years and underwent IVCCM, clinical and electrophysiologic examinations at baseline and follow up. At the end of follow up, participants were assigned as new-onset cases of DSP or as controls. Predictive validity was assessed using receiver operating characteristic curves. RESULTS: At baseline, participants were 34±15 years of age with mean diabetes duration of 18±12 years. The 11 (17%) new-onset cases of DSP were similar to the 54 (83%) controls in baseline age, diabetes duration, gender, glycated hemoglobin levels and electrophysiologic parameters (p≥0.20). However, cases of new onset had significantly lower baseline corneal nerve fibre length (CNFL) and branch density (p<0.05). For identification of new-onset cases, area under the receiver operating characteristic curve for CNFL was 0.78 with an optimal threshold of 14.9 mm/mm(2) (sensitivity=0.82, specificity=0.69). CONCLUSIONS: Despite similar clinical and electrophysiologic parameters, participants with type 1 diabetes at risk for future DSP had significantly lower baseline IVCCM measures. CNFL may have applicability in identifying high-risk patients for therapeutic intervention in clinical research and practice.


Subject(s)
Cornea/pathology , Diabetes Mellitus, Type 1/pathology , Diabetic Neuropathies/pathology , Adult , Canada , Diabetes Mellitus, Type 1/complications , Diabetic Neuropathies/complications , Electrophysiology , Female , Humans , Longitudinal Studies , Male , Microscopy, Confocal , Middle Aged , Predictive Value of Tests , ROC Curve
11.
Can J Diabetes ; 39(1): 50-4, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25175313

ABSTRACT

OBJECTIVE: Effectiveness of advanced technologies for diabetes management may differ depending on national healthcare models or population characteristics. In the setting of a cross-national trial, we aimed to compare efficacy of sensor-augmented pump (SAP) therapy in the United States (US) and Canada. METHODS: In the clinical trial Sensor-Augmented Pump Therapy for A1C Reduction (STAR 3), 329 adults with type 1 diabetes were randomly allocated to either SAP or glargine-based multiple daily injection (MDI) therapy at 26 US sites (n=271) and 4 Canadian sites (n=58). A bootstrap analysis was performed to confirm significant differences in baseline characteristics. For the primary analysis, we compared the baseline to 1-year change in glycated hemoglobin (A1C) between Canadian and US subjects. RESULTS: At baseline, compared with US subjects, Canadian subjects were more likely to be students (19% vs. 7%, p<0.01) and to consume alcohol (91% vs. 63%, p<0.01). Although Canadian subjects had greater A1C reductions from baseline compared with US subjects (p=0.02), the incremental benefit of SAP was similar in the US (SAP compared with MDI, -0.93%±0.73% vs. -0.31%±0.81%, p<0.001) and Canada (-1.14%±0.72% vs. -0.67%±0.71%, p<0.001). Mean sensor use was significantly higher in Canada than in the US (79% vs. 68% of the time, p<0.001). CONCLUSIONS: Despite differences in baseline characteristics and sensor adherence, SAP efficacy was similar between US and Canadian participants. As long as the intervention is administered with a similar level of expertise as was conducted in the trial, it is likely to be applicable in diverse clinical practice settings.


Subject(s)
Diabetes Mellitus, Type 1/drug therapy , Insulin Infusion Systems , Insulin/therapeutic use , Adolescent , Adult , Aged , Canada , Child , Female , Glycated Hemoglobin/metabolism , Humans , Injections , Insulin/administration & dosage , Male , Middle Aged , Socioeconomic Factors , Treatment Outcome , United States
12.
PLoS One ; 9(9): e106995, 2014.
Article in English | MEDLINE | ID: mdl-25216179

ABSTRACT

OBJECTIVE: Compared to recently-studied novel morphological measures, conventional small nerve fiber functional tests have not been systematically studied for identification of diabetic sensorimotor polyneuropathy (DSP). We aimed to determine and compare the diagnostic performance of cooling detection thresholds (CDT) in a cross-sectional type 1 diabetes cohort. RESEARCH DESIGN AND METHODS: 136 subjects with type 1 diabetes and 52 healthy volunteers underwent clinical and electrophysiological examination for DSP classification concomitantly with the Toronto Clinical Neuropathy Score (TCNS) and three small fiber function tests: CDT, heart rate variability (HRV), and laser doppler imaging of axon-mediated neurogenic flare responses to cutaneous heating (LDIFLARE). Area under the curve (AUC) and optimal thresholds were determined by receiver operating characteristic (ROC) curves in the type 1 diabetes cohort. RESULTS: Type 1 diabetes subjects were 42±17 years of age with mean HbA1c 7.9±1.7%. Fifty-nine (45%) met the case definition for DSP. CDT values were lowest in cases with DSP (18.3±8.4°C) compared to controls without DSP (28.4±3.5°C) and to healthy volunteers (29.6±1.8°C; p-value for both comparisons<0.0001). AUCCDT was 0.863 which was similar to AUCTCNS (0.858, p = 0.24) and AUCHRV (0.788, p = 0.05), but exceeded AUCLDIFLARE (0.750, p = 0.001). The threshold of <25.1°C was equivalent to the lower bound of the healthy volunteer 95% distribution [25.1, 30.8°C] and performed with 83% sensitivity and 82% specificity. CONCLUSIONS: Akin to novel small fiber morphological measures, CDT is a functional test that identifies DSP with very good diagnostic performance. These findings support further research that revisits the role of CDT in early DSP detection.


Subject(s)
Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 1/physiopathology , Diabetic Neuropathies/diagnosis , Diabetic Neuropathies/physiopathology , Sensorimotor Cortex/physiopathology , Sensory Thresholds/physiology , Adult , Diabetic Neuropathies/complications , Female , Humans , Male , ROC Curve
13.
PLoS One ; 9(1): e86515, 2014.
Article in English | MEDLINE | ID: mdl-24466129

ABSTRACT

BACKGROUND: Confirmation of diabetic sensorimotor polyneuropathy (DSP) relies on standard nerve conduction studies (NCS) performed in specialized clinics. We explored the utility of a point-of-care device (POCD) for DSP detection by nontechnical personnel and a validation of diagnostic thresholds with those observed in a normative database. RESEARCH DESIGN AND METHODS: 44 subjects with type 1 and type 2 diabetes underwent standard NCS (reference method). Two nontechnical examiners measured sural nerve amplitude potential (SNAP) and conduction velocity (SNCV) using the POCD. Reliability was determined by intraclass correlation coefficients (ICC [2], [1]). Validity was determined by Bland-Altman analysis and receiver operating characteristic curves. RESULTS: The 44 subjects (50% female) with mean age 56 ± 18 years had mean SNAP and SNCV of 8.0 ± 8.6 µV and 41.5 ± 8.2 m/s using standard NCS and 8.0 ± 8.2 µV and 49.9 ± 11.1 m/s using the POCD. Intrarater reproducibility ICC values were 0.97 for SNAP and 0.94 for SNCV while interrater reproducibility values were 0.83 and 0.79, respectively. Mean bias of the POCD was -0.1 ± 3.6 µV for SNAP and +8.4 ± 6.4 m/s for SNCV. A SNAP of ≤6 µV had 88% sensitivity and 94% specificity for identifying age-and height-standardized reference NCS values, while a SNCV of ≤48 m/s had 94% sensitivity and 82% specificity [corrected].. Abnormality in one or more of these thresholds was associated with 95% sensitivity and 71% specificity for identification of DSP according to electrophysiological criteria. CONCLUSIONS: The POCD demonstrated excellent reliability and acceptable accuracy. Threshold values for DSP identification validated those of published POCD normative values. We emphasize the presence of measurement bias--particularly for SNCV--that requires adjustment of threshold values to reflect those of standard NCS.


Subject(s)
Diabetic Neuropathies/diagnosis , Diabetic Neuropathies/physiopathology , Neural Conduction , Point-of-Care Systems , Sural Nerve/physiopathology , Adult , Aged , Female , Humans , Male , Middle Aged , ROC Curve , Reproducibility of Results
14.
Diabetes Care ; 36(9): 2748-55, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23579181

ABSTRACT

OBJECTIVE: In vivo corneal confocal microscopy (IVCCM) has been proposed as a noninvasive technique to assess small nerve fiber structural morphology. We investigated the structure-function relationship of small fibers in diabetic sensorimotor polyneuropathy (DSP). RESEARCH DESIGN AND METHODS: Ninety-six type 1 diabetic subjects with a spectrum of clinical DSP and 64 healthy volunteers underwent IVCCM examinations to determine corneal nerve structure, including corneal nerve fiber length (CNFL), fiber density (CNFD), branch density (CNBD), and fiber tortuosity (CNFT). Small nerve fiber function was assessed by cooling detection thresholds (CDTs), axon reflex-mediated neurogenic vasodilatation in response to cutaneous heating by laser Doppler imaging flare technique (LDIFLARE), and heart rate variability (HRV). Linear associations between structural and functional measures in type 1 diabetic subjects were determined using Spearman correlation coefficients and linear regression analysis. RESULTS: Of the type 1 diabetic subjects, with a mean age of 38.2 ± 15.5 years and a mean HbA1c of 7.9 ± 1.4%, 33 (34%) had DSP according to the consensus definition. Modest correlations were observed between CNFL, CNFD, and CNBD and all functional small-fiber tests (rs = 0.25 to 0.41; P ≤ 0.01 for all comparisons). For example, quantitatively every 1 mm/mm(2) lower CNFL was associated with a 0.61°C lower CDT, a 0.07 cm(2) lower LDIFLARE area, and a 1.78% lower HRV. No significant associations were observed for CNFT and the functional small-fiber measures. CONCLUSIONS: Small nerve fiber structural morphology assessed by IVCCM correlated well with functional measures of small nerve fiber injury. In particular, CNFL, CNFD, and CNBD demonstrated clear structure-function relationships.


Subject(s)
Cornea/innervation , Diabetes Mellitus, Type 1/pathology , Diabetic Neuropathies/pathology , Adult , Aged , Cornea/pathology , Female , Humans , Male , Microscopy, Confocal , Middle Aged , Young Adult
15.
PLoS One ; 8(3): e58783, 2013.
Article in English | MEDLINE | ID: mdl-23533591

ABSTRACT

OBJECTIVE: Evaluation of diabetic sensorimotor polyneuropathy (DSP) is hindered by the need for complex nerve conduction study (NCS) protocols and lack of predictive biomarkers. We aimed to determine the performance of single and simple combinations of NCS parameters for identification and future prediction of DSP. MATERIALS AND METHODS: 406 participants (61 with type 1 diabetes and 345 with type 2 diabetes) with a broad spectrum of neuropathy, from none to severe, underwent NCS to determine presence or absence of DSP for cross-sectional (concurrent validity) analysis. The 109 participants without baseline DSP were re-evaluated for its future onset (predictive validity). Performance of NCS parameters was compared by area under the receiver operating characteristic curve (AROC). RESULTS: At baseline there were 246 (60%) Prevalent Cases. After 3.9 years mean follow-up, 25 (23%) of the 109 Prevalent Controls that were followed became Incident DSP Cases. Threshold values for peroneal conduction velocity and sural amplitude potential best identified Prevalent Cases (AROC 0.90 and 0.83, sensitivity 80 and 83%, specificity 89 and 72%, respectively). Baseline tibial F-wave latency, peroneal conduction velocity and the sum of three lower limb nerve conduction velocities (sural, peroneal, and tibial) best predicted 4-year incidence (AROC 0.79, 0.79, and 0.85; sensitivity 79, 70, and 81%; specificity 63, 74 and 77%, respectively). DISCUSSION: Individual NCS parameters or their simple combinations are valid measures for identification and future prediction of DSP. Further research into the predictive roles of tibial F-wave latencies, peroneal conduction velocity, and sum of conduction velocities as markers of incipient nerve injury is needed to risk-stratify individuals for clinical and research protocols.


Subject(s)
Diabetic Neuropathies/physiopathology , Neural Conduction/physiology , Aged , Diabetes Mellitus, Type 1/physiopathology , Diabetes Mellitus, Type 2/physiopathology , Female , Humans , Male , Middle Aged
16.
J Diabetes Complications ; 27(3): 240-2, 2013.
Article in English | MEDLINE | ID: mdl-23266297

ABSTRACT

The consensus definition for diabetic sensorimotor polyneuropathy allows for subtle variation in specific diagnostic criteria. In 89 type 1 diabetes participants, we found that common variations in these criteria do not impact the diagnostic validity of corneal nerve fiber length, a parameter of corneal in vivo confocal microscopy.


Subject(s)
Cornea/pathology , Diabetes Mellitus, Type 1/complications , Diabetic Neuropathies/complications , Diabetic Retinopathy/diagnosis , Nerve Fibers/pathology , Polyneuropathies/complications , Adult , Biomarkers , Cohort Studies , Cornea/innervation , Diabetic Retinopathy/complications , Diabetic Retinopathy/pathology , Diagnostic Techniques, Ophthalmological , Female , Humans , Male , Microscopy, Confocal , Middle Aged , Reproducibility of Results , Sensitivity and Specificity
17.
Spine (Phila Pa 1976) ; 35(13): 1316-22, 2010 Jun 01.
Article in English | MEDLINE | ID: mdl-20354475

ABSTRACT

STUDY DESIGN: Retrospective review of consecutive case series. OBJECTIVE: To evaluate the early surgical results and complications of thoracic transdiscal osteotomies and vertebral shortening for the treatment of thoracic discitis/osteomyelitis. SUMMARY OF BACKGROUND DATA: Thoracic discitis/osteomyelitis leads to collapse of the disc space and/or vertebral body. We propose a novel technique to achieve the same goals as anterior column reconstruction through an entirely posterior approach. Shortening of the vertebral column provides structural support without the morbidity of an anterior approach. METHODS: Following REB approval, retrospective review of the charts of five patients that underwent posterior only thoracic transdiscal osteotomies and vertebral shortening for discitis/osteomyelitis was carried out. Posterior only surgery was performed in these patients with excision of the affected disc space and corresponding posterior elements. Instrumented fusion was performed across the segment spanning multiple vertebral levels. Clinical outcome, radiographic correction, and perioperative complications were analyzed. RESULTS: Three patients had bacterial discitis, and 2 had tuberculosis. Mean age at the time of surgery was 61 years (50-76). Mean follow-up was 45 months (25-63). There was no neurologic deterioration; 2 patients with Frankel grade B improved to grade D and E, respectively. Mean kyphosis corrected from 36 degrees (14-90) to 4 degrees (0-8), and the mean construct spanned 9 levels (6-15). No major complications were encountered during surgery. Two patients underwent revision surgeries, 1 patient died of unrelated causes at 6 months. All patients were treated with a full course of postoperative antibiotic treatment. No cases of recurrent infection were recorded. CONCLUSION: Thoracic transdiscal osteotomy with vertebral shortening is a safe and effective option for the treatment of infectious discitis/osteomyelitis with associated kyphosis. With adjuvant antibiotics, it effectively eradicates the infection through a posterior only approach, avoiding the need for anterior procedures and long anterior struts.


Subject(s)
Discitis/surgery , Osteomyelitis/surgery , Osteotomy/methods , Plastic Surgery Procedures/methods , Aged , Female , Follow-Up Studies , Humans , Male , Middle Aged , Outcome Assessment, Health Care , Retrospective Studies , Thoracic Vertebrae/pathology , Thoracic Vertebrae/surgery
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