Jack Lee

Reliability of Shear Wave Ultrasound Elastography for Neck Lesions Identified in Routine Clinical Practice

PURPOSE To evaluate the reliability of shear wave ultrasound elastography (SWE) in the neck. MATERIALS AND METHODS 176 neck lesions (40 thyroid, 56 lymph nodes, 46 salivary, 34 miscellaneous) identified in a routine US clinic underwent SWE by one or two blinded radiologists. For this study, SWE required the operator to acquire three 10 second dynamic colour-coded SWE cineloops per lesion, select one static image per cineloop, and place circular regions-of-interest within the entire lesion and stiffest part to generate 3 SWE measurements per static image. For logistical reasons, one radiologist evaluated all 176 lesions and the other evaluated 58 lesions. Both radiologists also reviewed 27 archived cineloops independently to assess SWE excluding practical technique. Reliability was assessed using intraclass correlation coefficients (ICCs) concordance correlation coefficients (CCCs) and coefficients of repeatability (CORs). RESULTS Test-retest ICCs for the radiologist evaluating 176 lesions were 0.78 - 0.85 (fair-excellent agreement), CCCs were 0.85 - 0.88 (substantial agreement), and CORs were 14.9 - 36.1 kPa. For both radiologists evaluating 58 lesions, intra-rater and inter-rater ICCs were 0.65 - 0.78 and 0.72 - 0.77 respectively. For SWE excluding practical technique, inter-rater ICCs were 0.97 - 0.98 (excellent agreement). ICCs differed according to tissue, being higher in thyroid lesions than lymph nodes (p < 0.001), and higher in benign than malignant lesions (p values < 0.001). CONCLUSION Intra- and inter-rater reliability of SWE is fair to excellent according to ICCs. SWE reliability is influenced appreciably by acquisition technique. Nevertheless, CORs for SWE are not negligible. To determine whether these results are acceptable clinically, further research is required to establish SWE stiffness values of normal and pathological tissues in the neck.

Detection of Neovascularization Based on Fractal and Texture Analysis with Interaction Effects in Diabetic Retinopathy

Diabetic retinopathy is a major cause of blindness. Proliferative diabetic retinopathy is a result of severe vascular complication and is visible as neovascularization of the retina. Automatic detection of such new vessels would be useful for the severity grading of diabetic retinopathy, and it is an important part of screening process to identify those who may require immediate treatment for their diabetic retinopathy. We proposed a novel new vessels detection method including statistical texture analysis (STA), high order spectrum analysis (HOS), fractal analysis (FA), and most importantly we have shown that by incorporating their associated interactions the accuracy of new vessels detection can be greatly improved. To assess its performance, the sensitivity, specificity and accuracy (AUC) are obtained. They are 96.3%, 99.1% and 98.5% (99.3%), respectively. It is found that the proposed method can improve the accuracy of new vessels detection significantly over previous methods. The algorithm can be automated and is valuable to detect relatively severe cases of diabetic retinopathy among diabetes patients.

Use of Rasch analysis in the evaluation of the oropharyngeal mucositis quality of life scale

Background:Oropharyngeal mucositis (OM) is a significant clinical problem causing profound impairment of health-related quality of life (HQoL) for patients undergoing cancer therapy. The Oropharyngeal Mucositis-Specific Health-Related Quality of Life Measure (OMQoL) was developed using classical test theory to measure the self-perceived HQoL of patients with mucositis. Objectives:The aim of this study was to analyze the OMQoL according to the Rasch model and, on the basis of results, determine whether improvements could be made. Method:A multicenter approach was used, and 210 patients treated with stomatotoxic chemotherapy (36%), high-dose myeloablative chemotherapy ± total body irradiation (10%), or head and neck irradiation ± chemotherapy (54%) completed the OMQoL. The Partial Credit Model of Rasch analysis was applied to evaluate the 31-item OMQoL using WINSTEPS and R software. Unidimensionality (measurement of a single construct), item fit, response category performance, person separation reliability, targeting of item difficulty to person ability, and differential item functioning (DIF) were examined. Results:Of 31 items, 5 were removed due to misfit; the OMQoL was reduced to 26 items with acceptable information weighted fit/outlier-sensitive fit indices (within 0.7-1.3) and eigenvalue units (≤2.0), confirming the unidimensionality of the reduced OMQoL. The OMQoL and its four subscales showed ordered category thresholds, and the person separation reliability was high (person separation index >0.2 with reliability >.8). Nevertheless, some of the items in the OMQoL might not be targeted effectively to patients with low levels of OM. Significant uniform and nonuniform DIFs were not found for gender (uniform DIF, p = .26; nonuniform DIF, p= .24) and age (uniform DIF, p = .95; nonuniform DIF, p = .65). Discussion:Rasch analysis reveals that the reduced 26-item OMQoL is unidimensional and is adequate to measure HQoL for patients with OM regardless of gender and age group. This improved version can provide a common platform for nurses to use in their assessment, caring, and treatment of patients with OM.

Functional Ability Improved in Essential Tremor by IncobotulinumtoxinA Injections Using Kinematically Determined Biomechanical Patterns – A New Future

Objective Effective treatment for functional disability caused by essential tremor is a significant unmet need faced by many clinicians today. Current literature regarding focal therapy by botulinum toxin type A (BoNT-A) injections uses fixed dosing regimens, which cannot be individualized, provides only limited functional benefit and unacceptable muscle weakness commonly occurs. This 38-week open label study, the longest to-date, demonstrates how kinematic technology addressed all these issues by guiding muscle selection. Method Participants (n = 24) were assessed at weeks 0, 6, 16, 22, 32, and 38 and injected with incobotulinumtoxinA at weeks 0, 16, and 32. Clinical assessments including UPDRS tremor items, Fahn-Tolosa-Marin (FTM) tremor rating scale assessing tremor severity, writing and functional ability, quality of life questionnaire (QUEST) and objective kinematic assessments were completed at every visit. Participants performed two postural and two weight-bearing scripted tasks with motion sensors placed over the wrist, elbow and shoulder joints. These sensors captured angular tremor amplitude (RMS units) and acceleration joint motion that was segmented into directional components: flexion-extension (F/E), pronation-supination and radial-ulnar at the wrist, F/E at the elbow, and F/E and adduction-abduction at the shoulder. Injection parameters were determined using kinematics, followed by the clinician’s determination of which muscles would contribute to the specific upper limb tremor biomechanics and dosing per participant. Results Multi-joint biomechanical recordings allowed individualized muscle selection and showed significant improvement in whole-arm function, FTM parts A-C scores, at week 6 which continued throughout the study. By week 38, the total FTM score statistically significantly reduced from 16.2±4.6 at week 0 to 9.5±6.3 (p<0.0005). UPDRS item 21 score rating action tremor was significantly reduced from 2.6±0.5 at week 0 to 1.6±1.1 (p = 0.01) at week 32. Quality of life (QUEST) significantly improved from 40.3±15.8 at week 0 to 31.1±15.3 (p = 0.035) at week 32 and to 27.8±15.3 (p = 0.028) at week 38. Kinematics provided an objective, secondary outcome measure, which showed a significant decrease in tremor amplitude in the wrist and shoulder joints (p<0.05). Eight participants (40%) self-reported mild weakness in injected muscles but had no interference in arm function. Conclusion Kinematic tremor assessments provide the injector unique insight to objectively individualize and personalize injection parameters demonstrating BoNT-A effectively alleviates functional disability caused by essential tremor. Kinematic technology is a promising method for standardizing assessments and for focal upper limb tremor treatment. Trial Registration ClinicalTrials.gov NCT02427646

Prospective Association between Diabetic Retinopathy and Cardiovascular Disease—A Systematic Review and Meta-analysis of Cohort Studies

BACKGROUND Diabetic retinopathy (DR) is linked to increased risk of cardiovascular (CV) disease. However, the effect size of the association was not consistent. In this study, we performed a systematic review and meta-analysis of available cohort studies to determine the association between DR and CV disease, and to investigate the factors that influence the association. METHODS Terms related to DR and CV disease were searched from MEDLINE and EMBASE database. High-quality articles (Newcastle-Ottawa scales above 6) conducted in cohort studies reporting the association between DR and CV disease were identified. Study-specific estimates were pooled using random effects with inverse variance meta-analysis. Subgroup analysis was performed according to diabetes types. Heterogeneity of included studies was assessed using the I(2) test. The cause of the heterogeneity was examined using metaregression analyses. RESULTS A total of 13 studies representing 17,611 patients without CV disease at baseline were included. At follow-up, there were 1457 CV disease-related incidences. Overall, DR was associated with increased risk of CV disease (relative risk [RR]: 2.42, 95% confidence interval [CI]: 1.77-3.31) in diabetes. Specifically, the RR was 3.59 (95% CI: 1.79-7.20) for type 1 diabetes and 1.81 (95% CI: 1.47-2.23) for type 2 diabetes. Significant heterogeneity was found in studies with type 1 diabetes. Metaregression analysis showed that baseline systolic blood pressure was a key factor leading to the heterogeneity. CONCLUSION In conclusion, DR is significantly associated with CV disease incidence and CV disease-related mortality in diabetes. Patients with DR may need more intensive management to control future CV disease attacks.

Long-term tremor therapy for Parkinson and essential tremor with sensor-guided botulinum toxin type A injections

Objective Current pharmacological agents used to treat Parkinson disease (PD) tremor and essential tremor (ET) provide suboptimal benefit and are commonly associated with significant adverse effects. Botulinum toxin type A (BoNT-A) has been shown to be effective for wrist tremor though functionally bothersome muscle weakness frequently occurs. This is the longest study to date demonstrating that BoNT-A therapy coupled with kinematic guidance can provide efficacious outcomes for upper limb tremor with minimized unwanted weakness. Methods A total of 28 PD and 24 ET participants with bothersome, disabling tremor, received six serial BoNT-A treatments every 16 weeks starting at week 0 with a follow-up visit 6 weeks following a treatment, totaling 96 weeks. Clinical scales, including Fahn-Tolosa-Marin tremor rating scale (FTM), and sensor-based tremor assessments were conducted at each visit. Kinematics was utilized to identify which arm muscles contributed to the tremulous movements and the experienced injector used clinical expertise in determining BoNT-A dosages. Results Following BoNT-A treatment, clinical ratings of tremor severity and functional ability (FTM) showed significant improvements following the first treatment which was maintained up to week 96 in PD and ET. Kinematics detected a significant reduction in PD and ET tremor amplitudes by 70% and 76% over the treatment course, respectively. By objectively distinguishing tremulous muscles and tremor severity, adverse effects were limited to mild perceived weakness by participants in injected muscles during follow-ups. Following the fourth treatment, BoNT-A dosages in flexor and extensor wrist muscles and biceps were reduced for those experiencing residual weakness which ultimately did not interfere with tremor relief or arm function. Conclusions Kinematics is an objective method that can aid clinicians in assessing and determining optimal BoNT-A parameters to alleviate both PD and ET tremor. BoNT-A injections are tolerable and effective when focal therapy regimens are determined and optimized kinematically over a long-term.

Increased prevalence of coronary plaque in patients with psoriatic arthritis without prior diagnosis of coronary artery disease

Objectives To evaluate coronary atherosclerosis in patients with psoriatic arthritis (PsA) and control subjects using coronary CT angiography (CCTA). Methods Ninety consecutive patients with PsA (male: 56(62.2%); 50.3±11.1 years) were recruited. 240 controls (male: 137(57.1%); 49.6±10.7 years) without known cardiovascular (CV) diseases who underwent CCTA due to chest pain and/or multiple CV risk factors were recruited for comparison. Results Patients with PsA and controls were matched in age, gender and traditional CV risk factors (all p>0.2). The prevalence of overall plaque (54(60%)/84(35%), p<0.001), calcified plaque (CP) (29(32%)/40(17%), p=0.002), mixed plaque (MP) (20(22%)/18(8%), p<0.001), non-calcified plaque (NCP) (39(43%)/53(22%), p<0.001) and combined MP/NCP (46(51%)/62(26%), p<0.001) were all significantly higher in patients with PsA. Three-vessel disease was diagnosed in 12(13%) patients with PsA and 7(3%) controls (p<0.001), while obstructive plaques (>50% stenosis) were observed in 8(9%) patients with PsA and 7(3%) controls (p=0.033). After adjusting for traditional CV risk factors, PsA remained an independent explanatory variable for all types of coronary plaques (OR: 2.730 to 4.064, all p<0.001). PsA was also an independent explanatory variable for three-vessel disease (OR: 10.798, p<0.001) and obstructive plaque (3.939, p=0.024). In patients with PsA, disease duration was the only disease-specific characteristic associated with more vulnerable plaques (MP/NCP) in multivariate analysis (1.063, p=0.031). The other independent explanatory variables were age ≥55 years (5.636, p=0.005) and male gender (8.197, p=0.001). Conclusions Patients with PsA have increased prevalence, burden and severity of coronary atherosclerosis as documented by CCTA. Longer disease duration was independently associated with the presence of vulnerable MP/NCP plaques in patients with PsA. Trial registration number NCT02232321.

Underestimation of Risk of Carotid Subclinical Atherosclerosis by Cardiovascular Risk Scores in Patients with Psoriatic Arthritis

Objective. To test the performances of established cardiovascular (CV) risk scores in discriminating subclinical atherosclerosis (SCA) in patients with psoriatic arthritis. Methods. These scores were calculated: Framingham risk score (FRS), QRISK2, Systematic COronary Risk Evaluation (SCORE), 10-year atherosclerotic cardiovascular disease risk algorithm (ASCVD) from the American College of Cardiology and the American Heart Association, and the European League Against Rheumatism (EULAR)–recommended modified versions (by 1.5 multiplication factor, m-). Carotid intima-media thickness > 0.9 mm and/or the presence of plaque determined by ultrasound were classified as SCA+. Results. We recruited 146 patients [49.4 ± 10.2 yrs, male: 90 (61.6%)], of whom 142/137/128/118 patients were eligible to calculate FRS/QRISK2/SCORE/ASCVD. Further, 62 (42.5%) patients were SCA+ and were significantly older, with higher systolic blood pressure and higher low-density lipoprotein cholesterol (all p < 0.05). All CV risk scores were significantly higher in patients with SCA+ [FRS: 7.8 (3.9–16.5) vs 2.7 (1.1–7.8), p < 0.001; QRISK2: 5.5 (3.1–10.2) vs 2.9 (1.2–6.3), p < 0.001; SCORE: 1 (0–2) vs 0 (0–1), p < 0.001; ASCVD: 5.6 (2.6–12.4) vs 3.4 (1.4–6.1), p = 0.001]. The Hosmer-Lemeshow test revealed moderate goodness of fit for the 4 CV scores (p ranged from 0.087 to 0.686). However, of the patients with SCA+, those identified as high risk were only 44.1% (by FRS > 10%), 1.8% (QRISK2 > 20%), 10.9% (SCORE > 5%), and 43.6% (ASCVD > 7.5%). By applying the EULAR multiplication factor, 50.8%/14.3%/14.5%/54.5% of the patients with SCA+ were identified as high risk by m-FRS/m-QRISK2/m-SCORE/m-ASCVD, respectively. EULAR modification increased the sensitivity of FRS and ASCVD in discriminating SCA+ from 44% to 51%, and 44% to 55%, respectively. Conclusion. All CV risk scores underestimated the SCA+ risk. EULAR–recommended modification improved the sensitivity of FRS and ASCVD only to a moderate level.

Transitioning from Unilateral to Bilateral Upper Limb Tremor Therapy for Parkinson’s Disease and Essential Tremor Using Botulinum Toxin: Case Series

Botulinum toxin type A (BoNT-A) injections guided by kinematic analysis for unilateral upper limb essential tremor (ET) and Parkinson’s disease (PD) tremor therapy has demonstrated efficacy, improvements in quality of life (QoL) and arm functionality. In this open-label pilot trial, 5 ET and 2 PD participants decided to switch from receiving long-term unilateral arm treatment to now bilateral BoNT-A arm therapy in their other tremulous arm which worsened over time. Injection patterns were based on kinematic analysis. Efficacy endpoints including kinematic analysis, Fahn-Tolosa-Marin tremor rating scale, QoL questionnaire, and maximal grip strength were collected over 2 treatments and 2 follow-up visits totaling 18-weeks. BoNT-A decreased wrist tremor amplitude by 84.6% and 89.6% 6-weeks following the 1st injection in the newly-treated limb in ET and PD participants, respectively. PD participants started with worse QoL but demonstrated an additional improvement in QoL by 29.9% for switching to bilateral treatment, whereas ET participants did not. Left and right arm tremor also did not share commonalities in severity or dose. This preliminary finding suggests trends for transitioning to bilateral therapy and warrants further studies to evaluate efficacy of bilateral tremor BoNT-A therapy in a larger cohort of PD and ET patients.

Bone Mass, Microstucture And Strength Can Discriminate Vertebral Fracture In Patients on Long-Term Steroid Treatment.

Context Measurement of areal bone mineral density (aBMD) by dual-energy x-ray absorptiometry (DXA) was able to predict fracture risk. High-resolution peripheral quantitative computed tomography (HR-pQCT) yields additional information about volumetric bone mineral density (vBMD), microarchitecture, and strength that may increase our understanding of fracture susceptibility. Objective To ascertain whether vBMD, microarchitecture, and estimated bone strength derived from HR-pQCT can discriminate vertebral fractures in patients with glucocorticoid-induced osteoporosis (GIOP) independent of aBMD. Design A cross-sectional case-control study. Setting Seven regional hospitals in Hong Kong. Patients A total of 110 patients on long-term glucocorticoids with vertebral fracture, determined radiographically, and 110 patients on long-term glucocorticoids without fracture. Main Outcome Measures We assessed vBMD, microarchitecture, and bone strength; aBMD; and fracture risk assessment tool (FRAX). Results Patients with vertebral fracture had lower total vBMD and a thinner cortex at the distal tibia after adjustment for age, sex, and aBMD or FRAX. In the antiresorptive treatment-naive subgroup, patients with vertebral fracture also had lower total vBMD at both the distal radius and the tibia after adjustment for covariates. Lower total vBMD and a thinner cortex were also noticed in the nonosteoporotic or FRAX score of <10% subgroups with vertebral fracture and were also associated with increasing prevalence of vertebral fracture. Conclusion Patients with GIOP and vertebral fracture have a significant reduction in total vBMD and cortical thinning independent of aBMD and FRAX. These changes may help identify high-risk patients in the subgroups currently considered to have low fracture risk as assessed by DXA or FRAX.