Thirty-Day Readmissions Are Largely Not Preventable in Patients With Cirrhosis.

INTRODUCTION: Hospital readmissions are common in patients with cirrhosis, but there are few studies describing readmission preventability. We aimed to describe the incidence, causes, and risk factors for preventable readmission in this population. METHODS: We performed a prospective cohort study of patients with cirrhosis hospitalized at a single center between June 2014 and March 2020 and followed up for 30 days postdischarge. Demographic, clinical, and socioeconomic data, functional status, and quality of life were collected. Readmission preventability was independently and systematically adjudicated by 3 reviewers. Multinomial logistic regression was used to compare those with (i) preventable readmission, (ii) nonpreventable readmission/death, and (iii) no readmission. RESULTS: Of 654 patients, 246 (38%) were readmitted, and 29 (12%) were preventable readmissions. Reviewers agreed on preventability for 70% of readmissions. Twenty-two (including 2 with preventable readmission) died. The most common reasons for readmission were hepatic encephalopathy (22%), gastrointestinal bleeding (13%), acute kidney injury (13%), and ascites (6%), and these reasons were similar between preventable and nonpreventable readmissions. Preventable readmission was often related to paracentesis timeliness, diuretic adjustment monitoring, and hepatic encephalopathy treatment. Compared with nonreadmitted patients, preventable readmission was independently associated with racial and ethnic minoritized individuals (odds ratio [OR] 5.80; 95% CI, 1.96-17.13), nonmarried marital status (OR 2.88; 95% CI, 1.18-7.05), and admission in the prior 30 days (OR 3.45; 95% CI, 1.48-8.04). DISCUSSION: For patients with cirrhosis, readmission is common, but most are not preventable. Preventable readmissions are often related to ascites and hepatic encephalopathy and are associated with racial and ethnic minorities, nonmarried status, and prior admissions.

Relationship between Intraocular Pressure Fluctuation and Visual Field Progression Rates in the United Kingdom Glaucoma Treatment Study.

PURPOSE: To investigate whether intraocular pressure (IOP) fluctuation is associated independently with the rate of visual field (VF) progression in the United Kingdom Glaucoma Treatment Study. DESIGN: Randomized, double-masked, placebo-controlled multicenter trial. PARTICIPANTS: Participants with ≥5 VFs (213 placebo, 217 treatment). METHODS: Associations between IOP metrics and VF progression rates (mean deviation [MD] and five fastest locations) were assessed with linear mixed models. Fluctuation variables were mean Pascal ocular pulse amplitude (OPA), standard deviation (SD) of diurnal Goldmann IOP (diurnal fluctuation), and SD of Goldmann IOP at all visits (long-term fluctuation). Fluctuation values were normalized for mean IOP to make them independent from the mean IOP. Correlated nonfluctuation IOP metrics (baseline, peak, mean, supine, and peak phasing IOP) were combined with principal component analysis, and principal component 1 (PC1) was included as a covariate. Interactions between covariates and time from baseline modeled the effect of the variables on VF rates. Analyses were conducted separately in the two treatment arms. MAIN OUTCOME MEASURES: Associations between IOP fluctuation metrics and rates of MD and the five fastest test locations. RESULTS: In the placebo arm, only PC1 was associated significantly with the MD rate (estimate, -0.19 dB/year [standard error (SE), 0.04 dB/year]; P < 0.001), whereas normalized IOP fluctuation metrics were not. No variable was associated significantly with MD rates in the treatment arm. For the fastest five locations in the placebo group, PC1 (estimate, -0.58 dB/year [SE, 0.16 dB/year]; P < 0.001), central corneal thickness (estimate, 0.26 dB/year [SE, 0.10 dB/year] for 10 µm thicker; P = 0.01) and normalized OPA (estimate, -3.50 dB/year [SE, 1.04 dB/year]; P = 0.001) were associated with rates of progression; normalized diurnal and long-term IOP fluctuations were not. In the treatment group, only PC1 (estimate, -0.27 dB/year [SE, 0.12 dB/year]; P = 0.028) was associated with the rates of progression. CONCLUSIONS: No evidence supports that either diurnal or long-term IOP fluctuation, as measured in clinical practice, are independent factors for glaucoma progression; other aspects of IOP, including mean IOP and peak IOP, may be more informative. Ocular pulse amplitude may be an independent factor for faster glaucoma progression. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Tablet-based tests of everyday visual function in a diabetic macular oedema (DME) clinic waiting area: A feasibility study.

PURPOSE: (1) To assess the feasibility of conducting tablet-based vision tests in hospital clinic waiting areas; (2) To test the hypothesis that increasing severity of diabetic macular oedema (DME) is associated with the performance of tablet-based surrogates of everyday tasks and self-reported visual function. METHODS: Sixty-one people with mild (n = 28), moderate (n = 24) or severe (n = 9) DME performed two tablet-based tests of 'real-world' visual function (visual search and face recognition) while waiting for appointments in a hospital outpatient clinic. Participants also completed a tablet-based version of a seven-item, visual-functioning (VF-7) patient-reported outcome measure. Test performance was compared to previously published 99% normative limits for normally sighted individuals. RESULTS: Thirty-four participants (56%; 95% confidence interval [CI] 43%-68%) exceeded normative limits for visual search, while eight (13%; 95% CI 65%-24%) exceeded normative limits for face discrimination. Search duration was significantly longer for people with severe DME than those with mild and moderate DME (p = 0.01). Face discrimination performance was not significantly associated with DME severity. VF-7 scores were statistically similar across DME severity groups. Median time to complete all elements (eligibility screening, both tablet-based tasks and the VF-7) was 22 (quartiles 19, 25) min. Further, 98% and 87% of participants, respectively, reported the search task and face discrimination task to be enjoyable, while 25% and 97%, respectively, reported finding the two tasks to be difficult. CONCLUSIONS: Portable tablet-based tests are quick, acceptable to patients and feasible to be performed in a clinic waiting area with minimal supervision. They have the potential to be piloted in patients' homes for self-monitoring.

Spatiotemporal summation of perimetric stimuli in healthy observers.

Spatial summation of perimetric stimuli has been used to derive conclusions about the spatial extent of retinal-cortical convergence, mostly from the size of the critical area of summation (Ricco's area, RA) and critical number of retinal ganglion cells (RGCs). However, spatial summation is known to change dynamically with stimulus duration. Conversely, temporal summation and critical duration also vary with stimulus size. Such an important and often neglected spatiotemporal interaction has important implications for modeling perimetric sensitivity in healthy observers and for formulating hypotheses for changes measured in disease. In this work, we performed experiments on visually heathy observers confirming the interaction of stimulus size and duration in determining summation responses in photopic conditions. We then propose a simplified computational model that captures these aspects of perimetric sensitivity by modelling the total retinal input, the combined effect of stimulus size, duration, and retinal cones-to-RGC ratio. We additionally show that, in the macula, the enlargement of RA with eccentricity might not correspond to a constant critical number of RGCs, as often reported, but to a constant critical total retinal input. We finally compare our results with previous literature and show possible implications for modeling disease, especially glaucoma.

Policy-Driven, Multimodal Deep Learning for Predicting Visual Fields from the Optic Disc and OCT Imaging.

PURPOSE: To develop and validate a deep learning (DL) system for predicting each point on visual fields (VFs) from disc and OCT imaging and derive a structure-function mapping. DESIGN: Retrospective, cross-sectional database study. PARTICIPANTS: A total of 6437 patients undergoing routine care for glaucoma in 3 clinical sites in the United Kingdom. METHODS: OCT and infrared reflectance (IR) optic disc imaging were paired with the closest VF within 7 days. EfficientNet B2 was used to train 2 single-modality DL models to predict each of the 52 sensitivity points on the 24-2 VF pattern. A policy DL model was designed and trained to fuse the 2 model predictions. MAIN OUTCOME MEASURES: Pointwise mean absolute error (PMAE). RESULTS: A total of 5078 imaging scans to VF pairs were used as a held-out test set to measure the final performance. The improvement in PMAE with the policy model was 0.485 (0.438, 0.533) decibels (dB) compared with the IR image of the disc alone and 0.060 (0.047, 0.073) dB with to the OCT alone. The improvement with the policy fusion model was statistically significant (P < 0.0001). Occlusion masking shows that the DL models learned the correct structure-function mapping in a data-driven, feature agnostic fashion. CONCLUSIONS: The multimodal, policy DL model performed the best; it provided explainable maps of its confidence in fusing data from single modalities and provides a pathway for probing the structure-function relationship in glaucoma.

Unrecognized cardiac arrests: A one-year review of audio from emergency medical dispatch calls.

OBJECTIVES: Immediate recognition of out-of-hospital cardiac arrest (OHCA) by Emergency Medical Dispatch (EMD) operators is crucial to facilitate timely initiation of telephone cardiopulmonary resuscitation (T-CPR) and to enable the appropriate level of Emergency Medical Services (EMS) response. The goal of this study was to identify patterns that can increase EMD-level recognition of cardiac arrests prior to EMS arrival. METHODS: The Combined Communications Center in Alachua County, Florida provided audio recordings of all emergency calls from January 1, 2018 to November 16, 2018 dispatched as a chief complaint other than OHCA, but later identified as cardiac arrest. A multi-disciplinary medical team transcribed and analyzed the calls to determine common themes and trends. RESULTS: Out of an initial 81 calls meeting inclusion criteria, 69 were immediately recognized as OHCA by EMDs, leaving 12 calls of unrecognized OHCA. In 11 of 12 calls respiratory issues were described to EMD. In 10 of 12 calls the subject was described as unconscious, and in the other 2 calls, the subject lost consciousness during the call. CONCLUSIONS: Lack of recognition of OHCA by EMD occurred in most calls due to difficulty communicating the subject's respiratory status. Further emphasis should be placed on identifying non-viable respirations in unconscious patients in EMD training and algorithms to increase recognition of OHCA and initiation of T-CPR. A multi-year review of a comparable dataset from geographically and socioeconomically diverse regions in the United States can validate and expand these preliminary trends.

Do Additional Testing Locations Improve the Detection of Macular Perimetric Defects in Glaucoma?

PURPOSE: To evaluate the ability of additional central testing locations to improve detection of macular visual field (VF) defects in glaucoma. DESIGN: Prospective cross-sectional study. PARTICIPANTS: Four hundred forty healthy people and 499 patients with glaucomatous optic neuropathy (GON) were tested with a fundus tracked perimeter (CMP; CenterVue) using a 24-2 grid with 12 additional macular locations (24-2+). METHODS: Glaucomatous optic neuropathy was identified based on expert evaluation of optic nerve head photographs and OCT scans, independently of the VF. We defined macular defects as locations with measurements outside the 5% and 2% normative limits on total deviation (TD) and pattern deviation (PD) maps within the VF central 10°. Classification was based on the total number of affected macular locations (overall detection) or the largest number of affected macular locations connected in a contiguous cluster (cluster detection). Criteria based on the number of locations and cluster size were used to obtain equivalent specificity between the 24-2 grid and the 24-2+ grids, calculated using false detections in the healthy cohort. Partial areas under the receiver operating characteristic curve (pAUCs) were also compared at specificities of 95% or more. MAIN OUTCOME MEASURES: Matched specificity comparison of the ability to detect glaucomatous macular defects between the 24-2 and 24-2+ grids. RESULTS: At matched specificity, cluster detection identified more macular defects with the 24-2+ grid compared with the 24-2 grid. For example, the mean increase in percentage of detection was 8% (95% confidence interval [CI], 5%-11%) and 10% (95% CI, 7%-13%) for 5% TD and PD maps, respectively, and 5% (95% CI, 2%-7%) and 6% (95% CI, 4%-8%) for the 2% TD and PD maps, respectively. Good agreement was found between the 2 grids. The improvement measured by pAUCs was also significant but generally small. The percentage of eyes with macular defects ranged from about 30% to 50%. Test time for the 24-2+ grid was longer (21% increase) for both cohorts. Between 74% and 98% of defects missed by the 24-2 grid had at least 1 location with sensitivity of < 20 dB. CONCLUSIONS: Visual field examinations with additional macular locations can improve the detection of macular defects in GON modestly without loss of specificity when appropriate criteria are selected.

Longitudinal Development of Peripapillary Hyper-Reflective Ovoid Masslike Structures Suggests a Novel Pathological Pathway in Multiple Sclerosis.

OBJECTIVE: Peripapillary hyper-reflective ovoid masslike structures (PHOMS) are a new spectral domain optical coherence tomography (OCT) finding. METHODS: This prospective, longitudinal study included patients (n = 212) with multiple sclerosis (MS; n = 418 eyes), 59 healthy controls (HCs; n = 117 eyes), and 267 non-MS disease controls (534 eyes). OCT and diffusion tensor imaging were used. RESULTS: There were no PHOMS in HC eyes (0/117, 0%). The prevalence of PHOMS was significantly higher in patients with MS (34/212, p = 0.001) and MS eyes (45/418, p = 0.0002) when compared to HCs (0/59, 0/117). The inter-rater agreement for PHOMS was 97.9% (kappa = 0.951). PHOMS were present in 16% of patients with relapsing-remitting, 16% of patients with progressive, and 12% of patients with secondary progressive disease course (2% of eyes). There was no relationship of PHOMS with age, disease duration, disease course, disability, or disease-modifying treatments. The fractional anisotropy of the optic radiations was lower in patients without PHOMS (0.814) when compared to patients with PHOMS (0.845, p = 0.03). The majority of PHOMS remained stable, but increase in size and de novo development of PHOMS were also observed. In non-MS disease controls, PHOMS were observed in intracranial hypertension (62%), optic disc drusen (47%), anomalous optic discs (44%), isolated optic neuritis (19%), and optic atrophy (12%). INTERPRETATION: These data suggest that PHOMS are a novel finding in MS pathology. Future research is needed to determine whether development of PHOMS in MS is due to intermittently raised intracranial pressure or an otherwise impaired "glymphatic" outflow from eye to brain. ANN NEUROL 2020;88:309-319.

Challenges, facilitators and barriers to screening study participants in early disease stages-experience from the MACUSTAR study.

BACKGROUND: Recruiting asymptomatic participants with early disease stages into studies is challenging and only little is known about facilitators and barriers to screening and recruitment of study participants. Thus we assessed factors associated with screening rates in the MACUSTAR study, a multi-centre, low-interventional cohort study of early stages of age-related macular degeneration (AMD). METHODS: Screening rates per clinical site and per week were compiled and applicable recruitment factors were assigned to respective time periods. A generalized linear mixed-effects model including the most relevant recruitment factors identified via in-depth interviews with study personnel was fitted to the screening data. Only participants with intermediate AMD were considered. RESULTS: A total of 766 individual screenings within 87 weeks were available for analysis. The mean screening rate was 0.6 ± 0.9 screenings per week among all sites. The participation at investigator teleconferences (relative risk increase 1.466, 95% CI [1.018-2.112]), public holidays (relative risk decrease 0.466, 95% CI [0.367-0.591]) and reaching 80% of the site's recruitment target (relative risk decrease 0.699, 95% CI [0.367-0.591]) were associated with the number of screenings at an individual site level. CONCLUSIONS: Careful planning of screening activities is necessary when recruiting early disease stages in multi-centre observational or low-interventional studies. Conducting teleconferences with local investigators can increase screening rates. When planning recruitment, seasonal and saturation effects at clinical site level need to be taken into account. TRIAL REGISTRATION: ClinicalTrials.gov NCT03349801 . Registered on 22 November 2017.

Innovation in resuscitation: A novel clinical decision display system for advanced cardiac life support.

INTRODUCTION: The Advanced Cardiac Life Support (ACLS) Clinical Decision Display System (CDDS) is a novel application designed to optimize team organization and facilitate decision-making during ACLS resuscitations. We hypothesized that resuscitation teams would more consistently adhere to ACLS guideline time intervals in simulated resuscitation scenarios with the CDDS compared to without. METHODS: We conducted a simulation-based, non-blinded, randomized, crossover-design study with resuscitation teams comprised of Emergency Medicine physicians, registered nurses, critical care technicians, and paramedics. Each team performed 4 ACLS scenarios in randomized sequences, half with the CDDS and half without. We analyzed the resuscitations and recorded the times of interventions that have defined intervals by ACLS: rhythm checks, epinephrine administration, and shock delivery. In addition, we surveyed each resuscitation team regarding their experience using the CDDS. RESULTS: On average, teams performed rhythm checks 4.9 s closer to ACLS guidelines with the CDDS (p = 0.0358). Teams were also more consistent; on average, teams reduced the variation of time between consecutive doses of epinephrine by 45% (p = 0.0001) and defibrillation by 47% (p < 0.0001). Ninety-eight percent of participants indicated they would use the CDDS if available in real cardiac arrests. CONCLUSIONS: This study demonstrates that the CDDS improves the accuracy and precision of timed ACLS interventions in a simulated setting. Resuscitation teams were strongly in favor of utilizing the CDDS in clinical practice. Further investigations of the introduction of the platform into real time clinical environments will be needed to assess true efficacy and patient outcomes.

Use of Composite End Points in Early and Intermediate Age-Related Macular Degeneration Clinical Trials: State-of-the-Art and Future Directions.

The slow progression of early age-related macular degeneration (AMD) stages to advanced AMD requires the use of surrogate end points in clinical trials. The use of combined end points may allow for shorter and smaller trials due to increased precision. We performed a literature search for the use of composite end points as primary outcome measures in clinical studies of early AMD stages. PubMed was searched for composite end points used in early/intermediate AMD studies published during the last 10 years. A total of 673 articles of interest were identified. After reviewing abstracts and applicable full-text articles, 33 articles were eligible and thus included in the qualitative synthesis. The main composite end point categories were: combined structural and functional end points, combined structural end points, combined functional end points and combined multicategorical end points. The majority of the studies included binary composite end points. There was a lack of sensitivity analyses of different end points against accepted outcomes (i.e., progression) in the literature. Various composite outcome measures have been used but there is a lack of standardization. To date no agreement on the optimal approach to implement combined end points in clinical studies of early stages of AMD exists, and no surrogate end points have been accepted for AMD progression.

Structural Endpoints and Outcome Measures in Uveitis.

Most uveitis entities are rare diseases but, taken together, are responsible for 5-10% of worldwide visual impairment which largely affects persons of working age. As with many rare diseases, there is a lack of high-level evidence regarding its clinical management, partly due to a dearth of reliable and objective quantitative endpoints for clinical trials. This review provides an overview of available structural outcome measures for uveitis disease activity and damage in an anatomical order from the anterior to the posterior segment of the eye. While there is a multitude of available structural outcome measures, not all might qualify as endpoints for clinical uveitis trials, and thorough testing of applicability is warranted. Furthermore, a consensus on endpoint definition, standardization, and "core outcomes" is required. As stipulated by regulatory agencies, endpoints should be precisely defined, clinically important, internally consistent, reliable, responsive to treatment, and relevant for the respective subtype of uveitis. Out of all modalities used for assessment of the reviewed structural outcome measures, optical coherence tomography, color fundus photography, fundus autofluorescence, and fluorescein/indocyanine green angiography represent current "core modalities" for reliable and objective quantification of uveitis outcome measures, based on their practical availability and the evidence provided so far.

Visual Field Outcomes from the Multicenter, Randomized Controlled Laser in Glaucoma and Ocular Hypertension Trial (LiGHT).

PURPOSE: To compare visual field outcomes of ocular hypertensive and glaucoma patients treated first with medical therapy with those treated first with selective laser trabeculoplasty (SLT). DESIGN: Secondary analysis of patients from the Laser in Glaucoma and Ocular Hypertension study, a multicenter randomized controlled trial. PARTICIPANTS: Three hundred forty-four patients (588 eyes) treated first with medical therapy and 344 patients (590 eyes) treated first with SLT. METHODS: Visual fields (VFs) were measured using standard automated perimetry and arranged in series (median length and duration, 9 VFs over 48 months). Hierarchical linear models were used to estimate pointwise VF progression rates, which were then averaged to produce a global progression estimate for each eye. Proportions of points and patients in each treatment group with fast (<-1 dB/year) or moderate (<-0.5 dB/year) progression were compared using log-binomial regression. MAIN OUTCOME MEASURES: Pointwise and global progression rates of total deviation (TD) and pattern deviation (PD). RESULTS: A greater proportion of eyes underwent moderate or fast TD progression in the medical therapy group compared with the SLT group (26.2% vs. 16.9%; risk ratio [RR], 1.55; 95% confidence interval [CI], 1.23-1.93; P < 0.001). A similar pattern was observed for pointwise rates (medical therapy, 26.1% vs. SLT, 19.0%; RR, 1.37; 95% CI, 1.33-1.42; P < 0.001). A greater proportion of pointwise PD rates were categorized as moderate or fast in the medical therapy group (medical therapy, 11.5% vs. SLT, 8.3%; RR, 1.39; 95% CI, 1.32-1.46; P < 0.001). No statistical difference was found in the proportion of eyes that underwent moderate or fast PD progression (medical therapy, 9.9% vs. SLT, 7.1%; RR, 1.39; 95% CI, 0.95, 2.03; P = 0.0928). CONCLUSIONS: A slightly larger proportion of ocular hypertensive and glaucoma patients treated first with medical therapy underwent rapid VF progression compared with those treated first with SLT.

Refinement and preliminary evaluation of two tablet-based tests of real-world visual function.

PURPOSE: To describe, refine, evaluate, and provide normative control data for two freely available tablet-based tests of real-world visual function, using a cohort of young, normally-sighted adults. METHODS: Fifty young (18-40 years), normally-sighted adults completed tablet-based assessments of (1) face discrimination and (2) visual search. Each test was performed twice, to assess test-retest repeatability. Post-hoc analyses were performed to determine the number of trials required to obtain stable estimates of performance. Distributions were fitted to the normative data to determine the 99% population-boundary for normally sighted observers. Participants were also asked to rate their comprehension of each test. RESULTS: Both tests provided stable estimates in around 20 trials (~1-4 min), with only a further reduction of 14%-17% in the 95% Coefficient of Repeatability (CoR95 ) when an additional 40 trials were included. When using only ~20 trials: median durations for the first run of each test were 191 s (Faces) and 51 s (Search); test-retest CoR95 were 0.27 d (Faces) and 0.84 s (Search); and normative 99% population-limits were 3.50 d (Faces) and 3.1 s (Search). No participants exhibited any difficulties completing either test (100% completion rate), and ratings of task-understanding were high (Faces: 9.6 out of 10; Search: 9.7 out of 10). CONCLUSIONS: This preliminary assessment indicated that both tablet-based tests are able to provide simple, quick, and easy-to-administer measures of real-world visual function in normally-sighted young adults. Further work is required to assess their accuracy and utility in older people and individuals with visual impairment. Potential applications are discussed, including their use in clinic waiting rooms, and as an objective complement to Patient Reported Outcome Measures (PROMs).

The circulating microbiome signature and inferred functional metagenomics in alcoholic hepatitis.

Intestinal dysbiosis is implicated in alcoholic hepatitis (AH). However, changes in the circulating microbiome, its association with the presence and severity of AH, and its functional relevance in AH is unknown. Qualitative and quantitative assessment of changes in the circulating microbiome were performed by sequencing bacterial DNA in subjects with moderate AH (MAH) (n = 18) or severe AH (SAH) (n = 19). These data were compared with heavy drinking controls (HDCs) without obvious liver disease (n = 19) and non-alcohol-consuming controls (NACs, n = 20). The data were related to endotoxin levels and markers of monocyte activation. Linear discriminant analysis effect size (LEfSe) analysis, inferred metagenomics, and predictive functional analysis using PICRUSt were performed. There was a significant increase in 16S copies/ng DNA both in MAH (P < 0.01) and SAH (P < 0.001) subjects. Compared with NACs, the relative abundance of phylum Bacteroidetes was significantly decreased in HDCs, MAH, and SAH (P < 0.001). In contrast, all alcohol-consuming groups had enrichment with Fusobacteria; this was greatest for HDCs and decreased progressively in MAH and SAH. Subjects with SAH had significantly higher endotoxemia (P = 0.01). Compared with alcohol-consuming groups, predictive functional metagenomics indicated an enrichment of bacteria with genes related to methanogenesis and denitrification. Furthermore, both HDCs and SAH showed activation of a type III secretion system that has been linked to gram-negative bacterial virulence. Metagenomics in SAH versus NACs predicted increased isoprenoid synthesis via mevalonate and anthranilate degradation, known modulators of gram-positive bacterial growth and biofilm production, respectively. CONCLUSION: Heavy alcohol consumption appears to be the primary driver of changes in the circulating microbiome associated with a shift in its inferred metabolic functions. (Hepatology 2018;67:1284-1302).

Are Patient Self-Reported Outcome Measures Sensitive Enough to Be Used as End Points in Clinical Trials?: Evidence from the United Kingdom Glaucoma Treatment Study.

PURPOSE: The United Kingdom Glaucoma Treatment Study (UKGTS) demonstrated the effectiveness of an intraocular pressure-lowering drug in patients with glaucoma using visual field progression as a primary outcome. The present study tested the hypothesis that responses on patient-reported outcome measures (PROMs; secondary outcome measure) differ between patients receiving a topical prostaglandin analog (latanoprost) or placebo eye drops in UKGTS. DESIGN: Multicenter, randomized, triple-masked, placebo-controlled trial. PARTICIPANTS: Newly diagnosed glaucoma patients in the UKGTS with baseline and exit PROMs (n = 182 and n = 168 patients from the treatment and placebo groups, respectively). METHODS: In the UKGTS (trial registration number, ISRCTN96423140), patients with open-angle glaucoma were allocated to receive latanoprost (treatment) or placebo; the observation period was 24 months. Patients completed general health PROMs (European Quality of Life in 5 Dimensions [EQ-5D] and 36-item Short Form [SF-36]) and PROMs specific to glaucoma (15-item Glaucoma Quality of Life [GQL-15] and 9-item Glaucoma Activity Limitation [GAL-9]) at baseline and exit from the trial. Percentage changes between measurement on PROMs were calculated for each patient and compared between treatment arms. In addition, differences between stable patients (n = 272) and those with glaucomatous progression (n = 78), as determined by visual field change (primary outcome), were assessed. MAIN OUTCOME MEASURE: PROMs on health-related and vision-related quality of life. RESULTS: Average percentage change on PROMs was similar for patients in both arms of the trial, with no statistically significant differences between treatment and placebo groups (EQ-5D, P = 0.98; EQ-5D visual analog scale, P = 0.88; SF-36, P = 0.94, GQL-15, P = 0.66; GAL-9, P = 0.87). There were statistically significant differences between stable and progressing patients on glaucoma-specific PROMs (GQL-15, P = 0.02; GAL-9, P = 0.02), but not on general health PROMs (EQ-5D, P = 0.62; EQ-5D visual analog scale, P = 0.23; SF-36, P = 0.65). CONCLUSIONS: Average change in PROMs on health-related and vision-related quality of life was similar for the treatment and placebo groups in the UKGTS. The PROMs used may not be sensitive enough to function as primary end points in clinical trials when participants have newly diagnosed early-stage glaucoma.

A Comparison between the Compass Fundus Perimeter and the Humphrey Field Analyzer.

PURPOSE: To evaluate relative diagnostic precision and test-retest variability of 2 devices, the Compass (CMP, CenterVue, Padova, Italy) fundus perimeter and the Humphrey Field Analyzer (HFA, Zeiss, Dublin, CA), in detecting glaucomatous optic neuropathy (GON). DESIGN: Multicenter, cross-sectional, case-control study. PARTICIPANTS: We sequentially enrolled 499 patients with glaucoma and 444 normal subjects to analyze relative precision. A separate group of 44 patients with glaucoma and 54 normal subjects was analyzed to assess test-retest variability. METHODS: One eye of recruited subjects was tested with the index tests: HFA (Swedish interactive thresholding algorithm [SITA] standard strategy) and CMP (Zippy Estimation by Sequential Testing [ZEST] strategy), 24-2 grid. The reference test for GON was specialist evaluation of fundus photographs or OCT, independent of the visual field (VF). For both devices, linear regression was used to calculate the sensitivity decrease with age in the normal group to compute pointwise total deviation (TD) values and mean deviation (MD). We derived 5% and 1% pointwise normative limits. The MD and the total number of TD values below 5% (TD 5%) or 1% (TD 1%) limits per field were used as classifiers. MAIN OUTCOME MEASURES: We used partial receiver operating characteristic (pROC) curves and partial area under the curve (pAUC) to compare the diagnostic precision of the devices. Pointwise mean absolute deviation and Bland-Altman plots for the mean sensitivity (MS) were computed to assess test-retest variability. RESULTS: Retinal sensitivity was generally lower with CMP, with an average mean difference of 1.85±0.06 decibels (dB) (mean ± standard error, P < 0.001) in healthy subjects and 1.46±0.05 dB (mean ± standard error, P < 0.001) in patients with glaucoma. Both devices showed similar discriminative power. The MD metric had marginally better discrimination with CMP (pAUC difference ± standard error, 0.019±0.009, P = 0.035). The 95% limits of agreement for the MS were reduced by 13% in CMP compared with HFA in participants with glaucoma and by 49% in normal participants. Mean absolute deviation was similar, with no significant differences. CONCLUSIONS: Relative diagnostic precision of the 2 devices is equivalent. Test-retest variability of MS for CMP was better than for HFA.

Healthy shopper? Blood pressure testing in a shopping centre Pop-Up in England.

BACKGROUND: Improving detection of elevated blood pressure (BP) remains a public health need. We present results from a Pop-Up health check stationed in shopping centres in England. We hypothesise the rate of case detection is related to measurable 'unhealthiness' of the shopping centres. METHODS: A Pop-Up health check was sited in four and three shopping centres sampled from the top ten unhealthiest and top 15 healthiest shopping regions respectively, following a report ranking towns/cities based on their unhealthy and healthy retail outlets. On one day in each shopping centre, people were approached and consented to BP testing. Outcome measure was people flagged with BP ≥ 140/90 mmHg (cases). RESULTS: We detected 45 (22.6%) and 20 (13.1%) cases from testing 199 and 152 adults in the unhealthy and healthy locations respectively (relative risk 1.72; 95% confidence interval: 1.06 to 2.78). A measure of unhealthy retail outlets (e.g. fast-food outlets) within each shopping centre was associated with detection rate (R2 = 0.61; p = 0.04). CONCLUSION: An association exists between cases of suspect hypertension found in a health check Pop-Up and measured 'unhealthiness' of the shopping centre site. Results hint at strategies for public testing of BP, potentially in the context of reducing health inequalities.

MACUSTAR: Development and Clinical Validation of Functional, Structural, and Patient-Reported Endpoints in Intermediate Age-Related Macular Degeneration.

PURPOSE: Currently, no outcome measures are clinically validated and accepted as clinical endpoints by regulatory agencies for drug development in intermediate age-related macular degeneration (iAMD). The MACUSTAR Consortium, a public-private research group funded by the European Innovative Medicines Initiative intends to close this gap. PROCEDURES: Development of study protocol and statistical analysis plan including predictive modelling of multimodal endpoints based on a review of the literature and expert consensus. RESULTS: This observational study consists of a cross-sectional and a longitudinal part. Functional outcome measures assessed under low contrast and low luminance have the potential to detect progression of visual deficit within iAMD and to late AMD. Structural outcome measures will be multimodal and investigate topographical relationships with function. Current patient-reported outcome measures (PROMs) are not acceptable to regulators and may not capture the functional deficit specific to iAMD with needed precision, justifying development of novel PROMs for iAMD. The total sample size will be n = 750, consisting mainly of subjects with iAMD (n = 600). CONCLUSIONS: As clinical endpoints currently accepted by regulators cannot detect functional loss or patient-relevant impact in iAMD, we will clinically validate novel candidate endpoints for iAMD.