Evaluation of meridional scans for angle closure assessment with anterior segment swept-source optical coherence tomography.

BACKGROUND/AIMS: As swept-source optical coherence tomography (SS-OCT) simultaneously obtains 128 meridional scans, it is important to identify which scans are playing the main role in classifying gonioscopic angle closure to simplify the analysis. We aimed to evaluate the diagnostic performance of every meridional scan in its ability to detect gonioscopic angle closure. METHODS: Observational study with 2027 phakic subjects consecutively recruited from a community polyclinic. Gonioscopy and SS-OCT were performed. Gonioscopic angle closure was defined as non-visibility of the posterior trabecular meshwork in ≥180° of the angle, while SS-OCT was defined as iridotrabecular contact anterior to the scleral spur. The area under the receiver operating characteristic curve (AUC) was calculated to assess the diagnostic performance of each single scan, the sequential anticlockwise cumulative effect of those single scans and different combinations of them. RESULTS: The AUCs of each scan ranged from 0.73 to 0.82. The single scan at 80°-260° had the highest AUC (0.82, 95% CI 0.79 to 0.84) and performed significantly better than most of the temporonasal scans (from 0° to 52° and from 153° to 179°). The superoinferior scans achieved higher AUCs compared with the temporonasal ones. When assessing the cumulative effect of adding individual scans consecutively, the peak AUC (0.80) was obtained when considering the superoinferior scans closer to 80°-85°, but no further positive cumulative effect was seen when adding the rest of the temporonasal scans of the circumference. CONCLUSIONS: In conclusion, the single SS-OCT scan at 80°-260° had the highest diagnostic performance. Our study suggests that the 360° evaluation may not translate to better clinical utility for detection of gonioscopic angle closure.

Longitudinal assessment of optic nerve head changes using optical coherence tomography in a primate microbead model of ocular hypertension.

In humans, the longitudinal characterisation of early optic nerve head (ONH) damage in ocular hypertension (OHT) is difficult as patients with glaucoma usually have structural ONH damage at the time of diagnosis. Previous studies assessed glaucomatous ONH cupping by measuring the anterior lamina cribrosa depth (LCD) and minimal rim width (MRW) using optical coherence tomography (OCT). In this study, we induced OHT by repeated intracameral microbead injections in 16 cynomolgus primates (10 unilateral; 6 bilateral) and assessed the structural changes of the ONH longitudinally to observe early changes. Elevated intraocular pressure (IOP) in OHT eyes was maintained for 7 months and serial OCT measurements were performed during this period. The mean IOP was significantly elevated in OHT eyes when compared to baseline and compared to the control eyes. Thinner MRW and deeper LCD values from baseline were observed in OHT eyes with the greatest changes seen between month 1 and month 2 of OHT. Both the mean and maximum IOP values were significant predictors of MRW and LCD changes, although the maximum IOP was a slightly better predictor. We believe that this model could be useful to study IOP-induced early ONH structural damage which is important for understanding glaucoma pathogenesis.

Understanding diagnostic disagreement in angle closure assessment between anterior segment optical coherence tomography and gonioscopy.

BACKGROUND/AIMS: Although being a more objective tool for assessment and follow-up of angle closure, reliability studies have reported a moderate diagnostic performance for anterior segment optical coherence tomography (OCT) technologies when comparing with gonioscopy as the reference standard. We aim to determine factors associated with diagnostic disagreement in angle closure when assessed by anterior segment swept source OCT (SS-OCT, CASIA SS-1000; Tomey, Nagoya, Japan) and gonioscopy. METHODS: Cross-sectional study. A total of 2027 phakic subjects aged ≥50 years, with no relevant previous ophthalmic history, were consecutively recruited from a community polyclinic in Singapore. Gonioscopy and SS-OCT (128 radial scans) for the entire circumference of the angle were performed for each subject. A two-quadrant closed gonioscopic definition was used. On SS-OCT images, angle closure was defined as iridotrabecular contact (ITC) to the extent of ≥35%, ≥50% and ≥75% of the circumferential angle. Diagnostic disagreements between both methods, that is, false positives or overcalls and false negatives or undercalls were defined, respectively, as gonioscopic open/closed angles inversely assessed as closed/open by SS-OCT. RESULTS: Two hundred and seventy-two (14.7%) resulted in overcall results (false positives) when ≥50% of the angle circumference was closed using SS-OCT. These eyes had significantly wider (anterior chamber width, 11.7 vs 11.6 mm, p<0.001) and deeper (anterior chamber depth (ACD), 2.4 vs 2.2 mm, p<0.001) anterior chambers than eyes assessed by both methods as closed (true positives). Deeper ACD (OR 9.31) and lower lens vault (LV) (OR 0.04) were significantly associated with a false positive diagnosis in the multivariate analysis. Most of these cases had short (52.6%) or irregular (39%) ITC in SS-OCT images. CONCLUSIONS: We found that anterior chamber dimensions, determined by ACD and LV, were factors significantly associated with diagnostic disagreement between anterior segment SS-OCT and gonioscopy in angle closure assessment.

Age-related changes in four-dimensional CMR-derived atrioventricular junction velocities and displacements: Implications for the identification of altered annular dynamics for ventricular function assessment.

BACKGROUND: We determined the age-related changes in atrioventricular junction (AVJ) velocities and displacements by feature tracking cardiovascular magnetic resonance (FT-CMR) in a healthy community-based population. We also investigated the importance of age-matching for the identification of altered AVJ dynamics. METHODS: FT-CMR was performed in 230 controls (18-78 years) and in two patient groups each consisting of 40 subjects (group 1: 23-55 years, group 2: 56-80 years). AVJ dynamic parameters, including systolic velocity Sm, early diastolic velocity Em, late diastolic velocity Am, maximal systolic excursion MAPSE and the new parameter sweep surface area velocity SSAV were measured. RESULTS: Increasing age in the control group was significantly associated with reductions in Sm, Em, MAPSE (r = -0.40, -0.76, -0.34, all P < 0.001) and an increase in Am (r = 0.45, P < 0.001). For patient group 1, the selection of an age-unmatched control group (56-76 years) underestimated the number of patients with abnormal AVJ dynamics during systole and early diastole (38% vs. 70% for Sm; 20% vs. 60% for Em; 35% vs. 50% for MAPSE). In contrast, for patient group 2, the number of patients with systolic and early diastolic AVJ dynamic abnormalities was overestimated (88% vs. 63% for Sm; 90% vs. 68% for Em; 73% vs. 58% for MAPSE) when compared with age-unmatched controls (24-55 years). Fifty-percent (20/40) of the sub-group of patients with normal left ventricular ejection fraction exhibited abnormal systolic Sm or MAPSE measurements. CONCLUSIONS: Significant correlations exist between age and AVJ dynamics. Age matching is important for evaluating AVJ long-axis function.

Defining a 'frequent admitter' phenotype among patients with repeat heart failure admissions.

AIMS: We aimed to identify a 'frequent admitter' phenotype among patients admitted for acute decompensated heart failure (HF). METHODS AND RESULTS: We studied 10 363 patients in a population-based prospective HF registry (2008-2012), segregated into clusters based on their 3-year HF readmission frequency trajectories. Using receiver-operating characteristic analysis, we identified the index year readmission frequency threshold that most accurately predicts HF admission frequency clusters. Two clusters of HF patients were identified: a high frequency cluster (90.9%, mean 2.35 ± 3.68 admissions/year) and a low frequency cluster (9.1%, mean 0.50 ± 0.81 admission/year). An index year threshold of two admissions was optimal for distinguishing between clusters. Based on this threshold, 'frequent admitters', defined as patients with ≥ 2 HF admissions in the index year (n = 2587), were of younger age (68 ± 13 vs 69 ± 13 years), more often male (58% vs. 54%), smokers (38.4% vs. 34.4%) and had lower left ventricular ejection fraction (37 ± 17 vs. 41 ± 17%) compared to 'non-frequent admitters' (< 2 HF admissions in the index year; n = 7776) (all P < 0.001). Despite similar rates of advanced care utilization, frequent admitters had longer length of stay (median 4.3 vs. 4.0 days), higher annual inpatient costs (€ 7015 vs. € 2967) and higher all-cause mortality at 3 years compared to the non-frequent admitters (adjusted odds ratio 2.33, 95% confidence interval 2.11-2.58; P < 0.001). CONCLUSION: 'Frequent admitters' have distinct clinical characteristics and worse outcomes compared to non-frequent admitters. This study may provide a means of anticipating the HF readmission burden and thereby aid in healthcare resource distribution relative to the HF admission frequency phenotype.

Management of hypertension and multiple risk factors to enhance cardiovascular health in Singapore: The SingHypertension cluster randomized trial.

BACKGROUND: Hypertension is a serious public health problem in Singapore and is associated with significant morbidity and mortality from cardiovascular disease (CVD) with considerable implications for health-care resources. The goal of the trial is to compare a multicomponent intervention (MCI) to usual care to evaluate the effectiveness and cost-effectiveness of the MCI for lowering blood pressure (BP) among adults with uncontrolled hypertension in Singapore primary-care clinics. METHODS/DESIGN: The study is a cluster randomized trial in eight polyclinics in Singapore: four deliver a structured MCI and four deliver usual care. The components of the MCI are: (1) an algorithm-driven antihypertensive treatment for all hypertensive individuals using single-pill combination (SPC) and lipid-lowering medication for high-risk hypertensive individuals, (2) a motivational conversation for high-risk hypertensive individuals, (3) telephone-based follow-ups of all hypertensive individuals by polyclinic nurses, and (4) discounts on SPC antihypertensive medications. The trial will be conducted with 1000 individuals aged ≥ 40 years with uncontrolled hypertension (systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg, based on the mean of the last two of three measurements) in eight polyclinics in Singapore. The primary outcome is change in systolic BP from baseline to follow-up at 24 months post-randomization. The incremental cost of MCI per CVD disability adjusted life years (DALY) averted and quality adjusted life years (QALY) saved will be computed. DISCUSSION: The demonstration of an effective and cost-effective hypertension control program that is implementable in busy polyclinics would provide compelling evidence for upscaling the program across all primary-care centers in Singapore, and possibly other regional countries with a similar health-care structure. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02972619 . Registered on 23 November 2016.

Factors Associated with Chronic Kidney Disease and Their Clinical Utility in Primary Care Clinics in a Multi-Ethnic Southeast Asian Population.

BACKGROUND: Chronic kidney disease (CKD) is a major global public health challenge. We investigated determinants of CKD and their clinical utility in an ethnically diverse Southeast Asian population. METHODS: Electronic health records (EHR) of adults ≥40 years who visited any one of 4 government polyclinics in Singapore from January 1, 2012 to -December 31, 2015 were analyzed. CKD was defined as an estimated glomerular filtration rate <60 mL/min/1.73 m2 or 1+ dipstick proteinuria excretion, based on 2 measurements ≥3 months apart. CKD-associated factors and their clinical utility for predicting odds of CKD were investigated using multiple logistic regression analysis. RESULTS: Based on the study criteria, 25.9% (95% CI 25.6-26.2) of the 88,765 eligible study individuals had CKD. The factors (OR and 95% CI) independently associated with CKD were older age ≥65 years (2.54 [2.44-2.64] vs. ≤65 years), respectively; men (1.13 [1.09-1.18]); Malay (1.27 [1.20-1.33]) and Indian (0.77 [0.71-0.83]) vs. Chinese ethnicity; overweight (body mass index [BMI] ≥27.5 kg/m2; 1.10 [1.04-1.16]) vs. normal weight (BMI 18 to <23 kg/m2); government (1.22 [1.15-1.31]) vs. private housing; and with hypertension (3.32 [3.09-3.56]), diabetes (6.93 [6.67-7.20]) or stroke (1.46 [1.36-1.56]) vs. without each co-morbidity, respectively. The area under the receiver operating characteristic curve (95% CI) for the model to predict the probability of CKD using hypertension, diabetes, and age was 0.808 (0.805-0.811). Only 28.5% (27.9-29.1%) of individuals with CKD had physician documentation of their CKD status. However, documentation of CKD status was associated with age ≥65 years (1.11 [1.04-1.20] vs. <65 years), men (1.35 [1.26-1.44]) vs. women, with vs. without hypertension (1.24 [1.07-1.44]), Indian (0.80 [0.69-0.92]) compared to Chinese ethnicity, ever smokers (0.89 [0.81-0.99]) vs. non-smokers, and those with vs. without stroke (0.83 [0.75-0.93]). CONCLUSIONS: CKD prevalence in our Southeast Asian population is high and under-documented even in high-risk patients. Our findings highlight factors associated with CKD, and the predictive value of hypertension, diabetes, and advancing age as EHR-based screening targets for CKD. Our results also suggest that complementary educational efforts will be needed to increase physician detection and optimize the management of CKD, especially in high risk and marginalized groups across all clinics in Singapore, and possibly in the region.

Evaluating the performance of National Comprehensive Cancer Network (NCCN) breast and ovarian genetic/familial high risk assessment referral criteria for breast cancer women in an Asian surgical breast clinic.

BACKGROUND: Globally, resources for genomic services vary. Current National Comprehensive Cancer Network (NCCN) breast and ovarian genetic/familial high risk assessment criteria for further genetic risk evaluation are useful, but lack specificity for reliably excluding patients with low a priori risk. This may result in patient overload in lesser-equipped genetics clinics. Since we use Manchester and the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) risk assessment models in our genetics clinic to determine whether genetic testing is warranted, we chose Manchester and BOADICEA as the reference standard to compare how the NCCN breast and ovarian genetic/familial high risk assessment criteria for further genetic risk evaluation performs against these two risk assessment models in referring breast cancer patients for genetic evaluation. METHODS: Breast cancer patients diagnosed from 2009-2011 were assessed using the NCCN criteria, Manchester and BOADICEA. Logistic regression and receiver operating characteristic (ROC) analysis were used to compare the NCCN criteria versus the Manchester and BOADICEA scoring systems in identifying high-risk patients. RESULTS: A total of 666 patients were included in the study. Percentages of high-risk patients resulting from Manchester and BOADICEA were 1.80% and 2.55%, respectively. Among the NCCN criteria, breast cancer and ≥1 close relatives with breast cancer at ≤50 years of age correlated best with Manchester and/or BOADICEA (c-statistic =0.831) with a false negative rate of 1.0%. CONCLUSIONS: Breast cancer at any age and ≥1 close relative with breast cancer at ≤50 years of age exhibited the highest correlation with Manchester and/or BOADICEA, promising greater specificity compared to the other NCCN criteria for segregating high risk, Asian breast cancer patients for referral to a genetics clinic, nevertheless recognizing the inherent limitations of the scoring systems.

Cup-to-Disc Ratio From Heidelberg Retina Tomograph 3 and High-Definition Optical Coherence Tomography Agrees Poorly With Clinical Assessment.

PURPOSE: To investigate the agreement of vertical cup-to-disc ratio (VCDR) measured from Heidelberg Retina Tomograph 3 (HRT-3), high-definition optical coherence tomography (HD-OCT), and clinical grading. METHODS: A total of 933 consecutive subjects underwent optic nerve head imaging with HRT-3 and HD-OCT during a single visit. The vertical dimensions of the disc and cup were measured by slit-lamp examination using an eyepiece graticule. Bland-Altman plots evaluated the agreement in the VCDR obtained by the 2 instruments and clinical grading. RESULTS: We found a significant trend for the difference in VCDR measured clinically and with HRT and HD-OCT (P<0.001 for both). The mean VCDR differed significantly between clinical measurement and that evaluated by HRT and HD-OCT, respectively (0.40 ± 0.12 vs. 0.37 ± 0.21 and 0.40 ± 0.12 vs. 0.50 ± 0.14, P<0.001 for both), with significantly poor correlation (r(2)=0.35 and 0.34, P<0.001 for both). CONCLUSIONS: In general, there is poor correlation and a lack of agreement of VCDR measured using HRT-3, HD-OCT, and clinical grading. HD-OCT has somewhat better agreement with clinical measurements of VCDR. Compared with clinical grading, HD-OCT tended to overestimate VCDR, whereas HRT-3 tended to underestimate it.

Estimating the potential savings with vagus nerve stimulation for treatment-resistant depression: a payer perspective.

OBJECTIVE: To provide a formula estimating potential reductions in healthcare utilization costs with adjunctive vagus nerve stimulation (VNS Therapy) in treatment-resistant depression (TRD). METHODS: This payer-perspective formula incorporates costs of treatment as usual for TRD patients from a published analysis of the MarketScan private payer claims database and the 2004 Medicare 5% standard analytic file. Estimated remission and response rates are from the published VNS pilot and pivotal studies. Costs were converted to 2008 US dollars per the US Bureau of Labor Statistics medical care costs, consumer price index. Device and implantation costs were calculated at $28,336. RESULTS: From the MarketScan and pooled outcomes data (VNS pilot and pivotal studies), potential per patient savings (hospitalization directly and indirectly related to depression) was $2974 at 5 years of device life, $23,539 at 8 years (moderate cost reduction scenario); $12,914 at 5 years, $40,935 at 8 years (optimistic scenario). Corresponding break-even device life was 4.57 and 3.62 years, respectively. From the Medicare file and pooled outcomes, potential per patient savings (inpatient and outpatient directly and indirectly related to depression) was $8358 at 5 years of device life, $32,385 at 8 years (moderate scenario); $19,837 at 5 years, $52,473 at 8 years (optimistic scenario). Corresponding break-even device life was 3.96 and 3.18 years, respectively. CONCLUSIONS: The formula allows an evaluation of expected reductions in healthcare costs as a function of input cost variables, efficacy rates, and benefit scenarios. Cited costs differ relative to care settings, diagnostic principles, and procedural volume. This formula can help assess moderate-to-longer-term economic benefits of VNS for a particular institution. Results suggested that potential reductions in healthcare costs with VNS for TRD may be substantial. Break-even device life for the scenarios presented ranges between 2.3 and 5.7 years.

Performance of delayed-enhancement magnetic resonance imaging with gadoversetamide contrast for the detection and assessment of myocardial infarction: an international, multicenter, double-blinded, randomized trial.

BACKGROUND: The identification and assessment of myocardial infarction (MI) are important for therapeutic and prognostic purposes, yet current recommended diagnostic strategies have significant limitations. We prospectively tested the performance of delayed-enhancement magnetic resonance imaging (MRI) with gadolinium-based contrast for the detection of MI in an international, multicenter trial. METHODS AND RESULTS: Patients with their first MI were enrolled in an acute (< or = 16 days after MI; n=282) or chronic (17 days to 6 months; n=284) arm and then randomized to 1 of 4 doses of gadoversetamide: 0.05, 0.1, 0.2, or 0.3 mmol/kg. Standard delayed-enhancement MRI was performed before contrast (control) and 10 and 30 minutes after gadoversetamide. For blinded analysis, precontrast and postcontrast MRIs were randomized and then scored for enhanced regions by 3 independent readers not associated with the study. The infarct-related artery perfusion territory was scored from x-ray angiograms separately. In total, 566 scans were performed in 26 centers using commercially available scanners from all major US/European vendors. All scans were included in the analysis. The sensitivity of MRI for detecting MI increased with rising dose of gadoversetamide (P<0.0001), reaching 99% (acute) and 94% (chronic) after contrast compared with 11% before contrast. Likewise, the accuracy of MRI for identifying MI location (compared with infarct-related artery perfusion territory) increased with rising dose of gadoversetamide (P<0.0001), reaching 99% (acute) and 91% (chronic) after contrast compared with 9% before contrast. For gadoversetamide doses > or = 0.2 mmol/kg, 10- and 30-minute images provided equal performance, and peak creatine kinase-MB levels correlated with MRI infarct size (P<0.0001). CONCLUSIONS: Gadoversetamide-enhanced MRI using doses of > or = 0.2 mmol/kg is effective in the detection and assessment of both acute and chronic MI. This study represents the first multicenter trial designed to evaluate an imaging approach for detecting MI.

Safety assessment of gadoversetamide (OptiMARK) administered by power injector.

PURPOSE: To evaluate the safety of OptiMARK (gadoversetamide injection) administered via power injector. MATERIALS AND METHODS: The study population included 144 healthy volunteers aged 18 years or older randomly assigned to one of seven treatment groups (N = 20/group). The safety assessment was based on changes in physical examination, vital signs, electrocardiograms (ECGs), standard clinical laboratory tests, and adverse events (AEs) through a 24-hour postinjection period. RESULTS: OptiMARK caused no serious AEs or unexpected changes in physical examinations or laboratory parameters. The changes observed in vital signs and ECG intervals did not vary with changes in injection rate and were not significantly (P < 0.05) different from those elicited by saline administration at the same rates. CONCLUSION: This study demonstrated the safety of OptiMARK when administered via a power injector at rates of 2, 4, and 6 mL/second.