Emulating Randomized Controlled Trials with Hybrid Control Arms in Oncology: A Case Study.

This proof-of-concept study retrospectively assessed the feasibility of applying a hybrid control arm design to a completed phase III randomized controlled trial (RCT; CheckMate-057) in advanced non-small cell lung cancer using a real-world data (RWD) source. The emulated trial consists of an experimental arm (patients from the RCT experimental cohort) and a hybrid control arm (patients from the RCT and RWD control cohorts). For the RWD control cohort, this study used a nationwide electronic health record-derived de-identified database. Three frequentist statistical borrowing methods were evaluated: a two-step Cox model, a fixed Cox model, and propensity score-integrated composite likelihood ("Methods 1-3"). The experimental treatment effect for hybrid control designs were evaluated using hazard ratios (HRs) with 95% confidence interval (CI) estimated from the Cox models accounting for covariate differences. The reduction in study duration compared to the RCT was also evaluated. All three statistical borrowing methods achieved comparable experimental treatment effects to that observed in the CheckMate-057 clinical trial, with HRs of 0.73 (95% CI: 0.59, 0.92), 0.74 (95% CI: 0.61, 0.91), 0.72 (95% CI: 0.59, 0.88) for Methods 1-3, respectively. Reduction in study duration time was 99-115 days when borrowing 30-38 events for Methods 1-3, respectively. This study demonstrated that it is feasible to emulate an RCT using a hybrid control arm design using three frequentist propensity-score based statistical borrowing methods. Selection of an appropriate, fit-for-use RWD cohort is critical to minimizing bias in experimental treatment effect.

Clinical utility of anti-interleukin 5 monoclonal therapy in asthma using a national, centralised, outcome-based system of drug access.

INTRODUCTION: Interleukin 5 (IL-5) inhibitors are an important therapeutic advance in the management of severe, refractory, eosinophilic asthma. However, their utilisation should be targeted to maximise their benefits. This study used multisite, centralised, national data collected over 18 months to perform an observational integrated, retrospective, cohort study of selection criteria for initiation and continuation of IL-5 inhibitor treatment in Ireland. MATERIALS/PATIENTS AND METHODS: We used data from 230 patients who were given anti-IL-5 monoclonal therapy (reslizumab, mepolizumab or benralizumab) in Ireland between 2018 and 2020. Reimbursement of these drugs in Ireland requires fulfilling eligibility criteria defined by the Acute Hospitals Drugs Management Programme with continued reimbursement requiring ongoing submission of clinical data demonstrating clinical effectiveness. RESULTS: IL-5 inhibitor use for 18 months was associated with a total reduction in asthma-associated hospital admissions of 108 (p=0.036) and in non-hospital exacerbations of 85 in 18 months (p=0.014). Respiratory-associated GP visits were reduced from 637 in 12 months to 89 at 6 months and 210 at 18 months of treatment (p<0.001). Oral corticosteroid requirement was reduced or stopped entirely (p<0.001). Subgroup analysis of one site replicated these results and showed a significant reduction in the Asthma Control Questionnaire Score (p<0.001) CONCLUSIONS: Selected patients continued on IL-5 treatment to 18 months had significantly reduced exacerbations, GP visits, oral corticosteroid use and asthma-associated hospitalisations. These results show that anti-IL-5 therapy, in carefully selected and monitored patients with asthma, results in significant improvements in clinical outcomes in a real-world setting.

Successful outcome using Tocilizumab in COVID-19 pneumonia with respiratory failure on a ward level.

We describe the case of a 40-year-old man of Asian ethnicity, who presented with one week history of shortness of breath, productive cough, intermittent hemoptysis, temperature, and systemic symptoms. He had a positive nasopharyngeal swab for SARS-CoV-2, standard COVID panel admission blood tests, a chest X-ray and a CT Pulmonary Angiogram. Significant bilateral infiltrates and no pulmonary embolism were identified. The patient received standard COVID-19 treatment. After 36 hours, he deteriorated requiring initiation of non-invasive ventilatory (NIV) support. In the context of worsening clinical status, the patient received Tocilizumab as a single dose with good clinical response. Early Tocilizumab intervention in appropriately selected patients should improve the outcome and length of hospitalization in COVID-19 pneumonia. It can be used as an intensive therapy unit sparing agent allowing management of critically ill patients on a ward-based level. This may further contribute to prevention of intensive therapy unit related complications and increased mortality.

Arthroscopic repair of inferior glenoid labrum tears (Down Under lesions) produces similar outcomes to other glenoid tears.

PURPOSE: Inferior glenoid labral tears are an uncommon but distinct shoulder injury. Only a small number of studies have reported outcomes following arthroscopic repair. The aim of the current study was to report minimum 2-year outcomes following inferior labral repair and to compare outcomes and risk factors associated with the injury to non-inferior labral tears. Whether preoperative MRI or MRA identified inferior labral tears was also assessed. METHODS: A prospective study of 162 consecutive patients undergoing arthroscopic glenoid labral repair, excluding isolated superior labral tears, was conducted. Of the 130 patients available for follow-up, 18 (13.7%) had an inferior labral tear ("Down Under lesion"), the remainder had anterior, posterior or mixed anterior/posterior lesions that did not include the inferior pole. Mean follow-up time for the Down Under group was 44 months (SD 10, range 27-57), and 30 months (SD 14, range 4-60) for the non-Down Under group. Postoperative outcomes included the Oxford Shoulder Instability Score and recurrent instability. Associations between Down Under lesions and injury mechanism, instability at presentation, recurrent instability and family history were assessed with multivariable logistic regression. Preoperative MRI or MRA reports by radiologists were examined to determine if Down Under lesions were identified. RESULTS: Oxford Shoulder Instability Scores indicated that most patients in both groups had little pain or shoulder problems postoperatively (average Oxford Score 41; 48 = no symptoms). Oxford Scores were not significantly different between the Down Under and non-Down Under groups. Four patients (22.2%) in the Down Under group had recurring symptoms (pain and instability) compared to 12 (10.6%) in the non-Down Under group; this difference was not statistically significant (adjusted OR 1.09, 95% CI 0.19,4.77). Family history of shoulder instability was positively associated with a Down Under lesion (adjusted OR 5.0, 95%CI 1.51,16.7). MRI or MRA identified 52.9% of Down Under lesions. CONCLUSION: Down Under lesions were an infrequent type of glenoid labral injury, yet postoperative outcomes were similar to other labral tears. Patients with Down Under lesions had a significant risk factor due to family history of shoulder instability. MRI and MRA could not reliably identify Down Under lesions. LEVEL OF EVIDENCE: Level III.

BioParts-A Biological Parts Search Portal and Updates to the ICE Parts Registry Software Platform.

Capturing, storing, and sharing biological DNA parts data are integral parts of synthetic biology research. Here, we detail updates to the ICE biological parts registry software platform that enable these processes, describe our implementation of the Web of Registries concept using ICE, and establish Bioparts, a search portal for biological parts available in the public domain. The Web of Registries enables standalone ICE installations to securely connect and form a distributed parts database. This distributed database allows users from one registry to query and access plasmid, strain, (DNA) part, plant seed, and protein entry types in other connected registries. Users can also transfer entries from one ICE registry to another or make them publicly accessible. Bioparts, the new search portal, combines the ease and convenience of modern web search engines with the capabilities of bioinformatics search tools such as BLAST. This portal, available at bioparts.org, allows anyone to search for publicly accessible biological part information (e.g., NCBI, iGEM, SynBioHub, Addgene), including parts publicly accessible through ICE Registries. Additionally, the portal offers a REST API that enables third-party applications and tools to access the portal's functionality programmatically.

Development and Validation of Risk Scores for All-Cause Mortality for a Smartphone-Based "General Health Score" App: Prospective Cohort Study Using the UK Biobank.

BACKGROUND: Given the established links between an individual's behaviors and lifestyle factors and potentially adverse health outcomes, univariate or simple multivariate health metrics and scores have been developed to quantify general health at a given point in time and estimate risk of negative future outcomes. However, these health metrics may be challenging for widespread use and are unlikely to be successful at capturing the broader determinants of health in the general population. Hence, there is a need for a multidimensional yet widely employable and accessible way to obtain a comprehensive health metric. OBJECTIVE: The objective of the study was to develop and validate a novel, easily interpretable, points-based health score ("C-Score") derived from metrics measurable using smartphone components and iterations thereof that utilize statistical modeling and machine learning (ML) approaches. METHODS: A literature review was conducted to identify relevant predictor variables for inclusion in the first iteration of a points-based model. This was followed by a prospective cohort study in a UK Biobank population for the purposes of validating the C-Score and developing and comparatively validating variations of the score using statistical and ML models to assess the balance between expediency and ease of interpretability and model complexity. Primary and secondary outcome measures were discrimination of a points-based score for all-cause mortality within 10 years (Harrell c-statistic) and discrimination and calibration of Cox proportional hazards models and ML models that incorporate C-Score values (or raw data inputs) and other predictors to predict the risk of all-cause mortality within 10 years. RESULTS: The study cohort comprised 420,560 individuals. During a cohort follow-up of 4,526,452 person-years, there were 16,188 deaths from any cause (3.85%). The points-based model had good discrimination (c-statistic=0.66). There was a 31% relative reduction in risk of all-cause mortality per decile of increasing C-Score (hazard ratio of 0.69, 95% CI 0.663-0.675). A Cox model integrating age and C-Score had improved discrimination (8 percentage points; c-statistic=0.74) and good calibration. ML approaches did not offer improved discrimination over statistical modeling. CONCLUSIONS: The novel health metric ("C-Score") has good predictive capabilities for all-cause mortality within 10 years. Embedding the C-Score within a smartphone app may represent a useful tool for democratized, individualized health risk prediction. A simple Cox model using C-Score and age balances parsimony and accuracy of risk predictions and could be used to produce absolute risk estimations for app users.

Ten-year safety follow-up and post-explant analysis of an anterior chamber phakic IOL.

PURPOSE: To assess endothelial cell loss (ECL) rate and collect safety data in patients with AcrySof L-series Cachet phakic intraocular lens (pIOL) up to 10 years post-implantation. SETTING: Clinical settings in the United States, European Union, and Canada. DESIGN: Nonrandomized, observational, open-label safety study. METHODS: Central and peripheral endothelial cell density was evaluated and compared with 6-month post-implantation baseline. Nonlinear analysis was performed to identify factors affecting post-explantation ECL. Additional evaluations included uncorrected visual acuity (UCVA), corrected distance visual acuity (CDVA), adverse device effects (ADEs), and serious adverse events (SAEs). RESULTS: The study included 1123 implanted eyes (mean age, 37.5 years). At 10 years, mean central and peripheral ECL was 16% (1.7% annualized). Explantations were performed in 10% of eyes (n = 136/1323). For eyes with pIOL explantation because of ECL (7%), annualized ECL rate post-explantation was numerically lower compared with the overall rate in eyes that underwent explantation for any reason (annualized rate, -1.65% vs -2.03%, respectively; n = 96) and compared with pre-explantation ECL. Mean ± SD CDVA and UCVA were -0.12 ± 0.11 and 0.03 ± 0.22 logarithm of the minimum angle of resolution, respectively. Common ocular ADEs included ECL (10%), pIOL extraction (9%), iris adhesion (7%), and pupillary deformity (2%). Common SAEs included pIOL extraction (11%), ECL (9%), and iris adhesions (8%). CONCLUSIONS: Cachet pIOLs were associated with long-term ECL in some cases. Overall, only 10% of all implanted eyes underwent explantation during 10-year follow-up. In patients requiring explantation because of ECL, the annualized ECL rates decreased post-explantation in some eyes. Continued monitoring of patients regardless of explantation is recommended.

Evaluating Rotational Stability of an Extended Depth of Focus Toric Intraocular Lens Using a Slit Lamp and Image-Based Analysis.

PURPOSE: To evaluate the rotational stability of a toric extended depth of focus (EDOF) intraocular lens (IOL), using either slit lamp evaluation or image-processing software. SETTING: Three clinical practices in the USA. DESIGN: Prospective unmasked randomized clinical trial. METHODS: Subjects presenting for routine cataract surgery that were interested in improved near vision received toric EDOF lenses (TECNIS Symfony® Toric) in both eyes. The measures of interest in the current analysis were the change in orientation of the IOL between 1 day, 1 month and 3 months postoperative. Orientation was measured at the microscope on the day of surgery, and with the slit lamp at all other visits. Day 1, 1-month and 3-month images of the lens orientation were captured with a slit lamp camera. Differences in orientation were recorded and analyzed. RESULTS: A total of 150 eyes had IOL orientation data available. Image analysis showed mean absolute lens orientation changes from 1 day to 1 month and 3 months of less than 2 degrees. The percentage of lenses exhibiting rotation of ≤5 degrees between any measured time points was 97% or higher. Results were similar, but significantly more variable, when IOL orientation was measured at the slit lamp. CONCLUSION: The toric EDOF lens evaluated here demonstrated rotational stability that exceeded the prior ANSI standard. The best method to determine IOL orientation changes was through image analysis. .

Defocus Curve and Patient Satisfaction with a New Extended Depth of Focus Toric Intraocular Lens Targeted for Binocular Emmetropia or Slight Myopia in the Non-Dominant Eye.

PURPOSE: To evaluate the defocus curve and patient satisfaction after implantation of an extended depth of focus (EDOF) toric IOL when both eyes were targeted for emmetropia and when the non-dominant eye was targeted for mini monovision (-0.50D). METHODS: A prospective unmasked randomized clinical trial in three clinical practices in the USA. Subjects presenting for routine cataract surgery were assigned to one of two groups, both receiving bilateral toric EDOF lenses. One group had the non-dominant eye targeted for slight myopia (-0.50D). Measures of interest were the postoperative defocus curve and reported patient satisfaction and visual disturbances. RESULTS: Questionnaire and defocus curve data were available from 37 subjects in the Emmetropia group, while the mini monovision group included questionnaire data from 39 subjects and valid defocus curve data from 14 subjects. Mini monovision subjects had significantly better VA (a half line to a line better, p < 0.05), from a defocus of -1.50 D to -3.00 D. Reported spectacle wear and satisfaction were not significantly different between groups at any distance, but more patients in the mini monovision group reported the ability to function comfortably without glasses at near and overall (near p = 0.02, overall p < 0.01). Halos and starbursts were the two phenomena reported most often for both groups, with reported starbursts slightly more common in the mini monovision group. CONCLUSIONS: A slightly myopic correction in the non-dominant eye improved binocular near vision by 0.5 to 1.0 lines based on defocus curve data. Patients reported better functional vision, but with a slight increase in reported starbursts in the mini monovision group.

Serious Asthma Outcomes and Asthma Exacerbations with Maintenance on Inhaled Corticosteroid (Mometasone Furoate)/Long-Acting Beta Agonist (Formoterol) Combination Compared to Step Down to Mometasone Monotherapy.

BACKGROUND: Because of historical safety concerns with the use of long-acting ß-agonists (LABA) in asthma, step-down from inhaled corticosteroid (ICS)/LABA combination therapy to ICS monotherapy is recommended once asthma control is achieved. OBJECTIVE: To evaluate the benefit/risk question about whether patients with asthma who achieve disease control on fixed-dose ICS/LABA combination therapy, such as mometasone furoate/formoterol fumarate (MF/F), should continue with this therapy or be stepped down to ICS monotherapy, such as MF. METHODS: Using data from 8447 clinically stable patients with persistent asthma in the Safety Pharma Investigation of Respiratory Outcomes trial who had been receiving a stable dose of ICS/LABA for ≥4 weeks, this post hoc analysis evaluated the risk of serious asthma outcomes (SAOs) (adjudicated hospitalization, intubation, or death) and asthma exacerbation (AEX) (composite of hospitalizations ≥24 hours, emergency visits <24 hours requiring systemic corticosteroid, or systemic corticosteroid for ≥3 consecutive days) in participants randomized to remain on ICS/LABA (MF/F) or step down to ICS (MF) for 26 weeks. RESULTS: There was no significant difference in SAO risk among patients maintained on ICS/LABA with MF/F compared with those who stepped down from ICS/LABA to MF (hazard ratio [HR], 1.03 [95% confidence interval (CI): 0.61, 1.75], P = .913). The risk of AEX was significantly lower in patients maintained on ICS/LABA with MF/F compared with those who stepped down from ICS/LABA to MF (HR, 0.87 [95% CI: 0.78, 0.98], P = .020). CONCLUSIONS: In this post hoc analysis of a large clinical trial dataset, maintenance on ICS/LABA with MF/F is not associated with an increased risk of SAOs and also significantly reduces the risk of AEX compared with step-down from ICS/LABA to MF.

Assessing research capacity in Victoria's south-west health service providers.

OBJECTIVE: To investigate the research interest, capacity and culture in individuals, teams and health organisations across south-western Victoria. DESIGN: Cross-sectional survey. SETTING: Eight public health services in the south-western region of Victoria. PARTICIPANTS: All staff were invited to participate. INTERVENTION: Hospital staff survey. MAIN OUTCOME MEASURE: The Research Capacity and Culture tool. RESULTS: The survey was completed by 776 staff including nurses, allied health staff and doctors. Half of the respondents were currently involved in research, while most wanted to be more involved. Respondents reported having moderate research skills and success at individual, team and organisation levels. Women and nurses reported having lower skills than comparable groups. Motivators for undertaking research were skill development (increased job satisfaction and brain stimulation) while the most commonly selected barriers were lack of time, other work taking priority and lack of funding. CONCLUSION: Health organisations in regional and rural Victoria could harness opportunities to enable staff participation in research by supporting identified strengths, addressing barriers and providing "permission" for staff to get involved in research. Efforts to improve research capacity among women and nurses could lead to the greatest overall improvement in organisations' research capacity and output-and translation of evidence into practice.

Extended depth-of-focus toric intraocular lens targeted for binocular emmetropia or slight myopia in the nondominant eye: Visual and refractive clinical outcomes.

PURPOSE: To compare the visual and refractive outcomes with a diffractive toric extended depth-of-focus (EDOF) intraocular lens (IOL) when both eyes are targeted for emmetropia and the nondominant eye is targeted for slight myopia. SETTING: Three clinical practices, United States. DESIGN: Prospective case series. METHODS: Patients having routine cataract surgery with bilateral Tecnis Symfony toric EDOF IOL implantation were assigned to 1 of 2 groups. In 1 group, the nondominant eye was targeted for -0.50 diopter (D) (mini-monovision). Assessments included uncorrected monocular and binocular visual acuities (logarithm of the minimum angle of resolution) at distance (4 m), intermediate (66 cm), and near (40 cm) and the postoperative residual refractive error. RESULTS: Forty patients were enrolled in each group, with 1 dropout. The mean postoperative residual refractive astigmatism was 0.25 D in both groups, with no statistically significant difference. The mean residual refractive astigmatism was 0.50 D or lower in 92% of eyes (72/78) in the mini-monovision group and 95% of eyes (74/78) in the emmetropia group 3 months postoperatively. The mini-monovision group had slightly worse uncorrected visual acuity at 4 m than the emmetropia group (0.16 versus 0.09; P = .002) but better uncorrected acuity at 40 cm (0.25 versus 0.34; P < .001). Binocular uncorrected acuity was not statistically significantly different between groups at 4 m (-0.03 versus -0.01; P = .33) or 66 cm (0.06 versus 0.04; P = .34) but was statistically significant at 40 cm (0.25 versus 0.19; P = .03). CONCLUSIONS: The EDOF toric IOL provided functional distance, intermediate, and near vision. A slight monovision approach appears to improve near visual acuity.

Corneal Endothelial Cell Loss and Morphometric Changes 5 Years after Phacoemulsification with or without CyPass Micro-Stent.

PURPOSE: To characterize long-term changes in corneal endothelial cells after phacoemulsification with or without supraciliary Micro-Stent (Alcon) implantation in eyes with open-angle glaucoma (OAG) and visually significant cataract. DESIGN: Three-year safety extension of a 2-year randomized clinical trial. METHODS: Patients from the multicenter Study of an Implantable Device for Lowering Intraocular Pressure in Glaucoma Patients Undergoing Cataract Surgery (COMPASS) trial who underwent Micro-Stent implantation plus phacoemulsification (n = 282) or phacoemulsification alone (n = 67) were analyzed post hoc. Specular microscopy was used to assess endothelial cell loss (ECL), including changes from baseline in endothelial cell density (ECD), coefficient of variation, and percentage of hexagonal cells. RESULTS: Preoperative ECDs in the microstent group (2,432.6 cells/mm2 [95% confidence interval [CI], 2,382.8-2,482.4 cells/mm2]) were similar to those in the control group (2,434.5 cells/mm2 [95% CI, 2,356.5-2,512.4 cells/mm2]) groups. ECL at months 48 and 60 was greater in the Micro-Stent group than in the control group. At month 60, the mean percent of changes in ECD was -20.4% (95% CI, -23.5% to -17.5%) in the Micro-Stent group and -10.1% (95% CI, -13.9% to -6.3%) in the control group. No statistically significant between-group changes from baseline in cellular morphology were observed. Nine adverse events were possibly related to ECL, including 3 eyes with transient focal corneal edema and 4 eyes that required Micro-Stent trimming due to protrusion. CONCLUSIONS: In eyes with OAG, ECL after phacoemulsification is acute and stabilizes after 3 months, whereas ECL after phacoemulsification plus Micro-Stent implantation proceeds for at least 5 years. Clinical findings associated with ECL in these eyes were uncommon (3.3% of implanted eyes), suggesting that ECL is generally a subclinical phenomenon.

Safety and Effectiveness of CyPass Supraciliary Micro-Stent in Primary Open-Angle Glaucoma: 5-Year Results from the COMPASS XT Study.

PURPOSE: To characterize the long-term (up to 5 years) safety and effectiveness of the supraciliary Micro-Stent (Alcon) implanted at the time of phacoemulsification in eyes with coexisting open-angle glaucoma (OAG) and visually significant cataract. DESIGN: Three-year safety extension of a 2-year randomized clinical trial. METHODS: Patients from the multicenter Study of an Implantable Device for Lowering Intraocular Pressure in Glaucoma Patients Undergoing Cataract Surgery (COMPASS) trial who underwent Micro-Stent implantation plus phacoemulsification (n = 215) or phacoemulsification alone (n = 67) were evaluated 36, 48, and 60 months postoperatively. The primary outcome measurement was the occurrence of sight-threatening ocular adverse events. Evaluations at each time point included best-corrected visual acuity (BCVA), anterior and posterior segment examinations, tonometry, gonioscopy, pachymetry, perimetry, specular microscopy, and assessment of adverse events. RESULTS: Three sight-threatening ocular adverse events occurred, 2 in the Micro-Stent group and 1 in the control group, but none of these events was related to the Micro-Stent device. Ocular adverse events were of similar frequencies in both groups, the most common of which were BCVA loss of ≥2 lines compared with best BCVA in COMPASS and worsening of visual field mean defect (VFMD) ≥2.5 dB compared with month 24. Changes in mean BCVA from baseline, clinical examinations, pachymetry, and VFMD were similar in the 2 groups. At 60 months, a higher proportion of subjects in the Micro-Stent group (46%; 95% confidence interval [CI], 38.9%-53.2%) than in the control group (32.1%; 95% CI 19.9%-46.3%) were able to achieve a reduction of ≥20% in intraocular pressure without using hypotensive medication. CONCLUSIONS: Few sight-threatening serious ocular adverse events occurred following Micro-Stent implantation, and clinical evidence of corneal decompensation was minimal.

Quantitative phase microscopy with enhanced contrast and improved resolution through ultra-oblique illumination (UO-QPM).

Recent developments in phase contrast microscopy have enabled the label-free visualization of certain organelles due to their distinct morphological features, making this method an attractive alternative in the study of cellular dynamics. However tubular structures such as endoplasmic reticulum (ER) networks and complex dynamics such as the fusion and fission of mitochondria, due to their low phase contrast, still need fluorescent labeling to be adequately imaged. In this article, we report a quantitative phase microscope with ultra-oblique illumination that enables us to see those structures and their dynamics with high contrast for the first time without labeling. The imaging capability was validated through comparison to the fluorescence images with the same field-of-view. The high image resolution (~270 nm) was validated using both beads and cellular structures. Furthermore, we were able to record the vibration of ER networks at a frame rate of 250 Hz. We additionally show complex cellular processes such as remodeling of the mitochondria networks through fusion and fission and vesicle transportation along the ER without labels. Our high spatial and temporal resolution allowed us to observe mitochondria "spinning", which has not been reported before, further demonstrating the advantages of the proposed method.

Objective Classification of mTBI Using Machine Learning on a Combination of Frontopolar Electroencephalography Measurements and Self-reported Symptoms.

BACKGROUND: The reliable diagnosis of a mild traumatic brain injury (mTBI) is a pervasive problem in sports and in the military. The frequency and severity of each occurrence, while difficult to quantify, may impact long term cognitive function and quality of life. Despite the new revelations concerning brain disfunction from head injuries, individuals still feel pressure to remain on the field despite a debilitating injury. In this study, we evaluated the accuracy of a system that could be employed on the sidelines or in the locker room to provide an immediate objective mTBI assessment. METHODS: Participants consisted of 38 individuals with a recent mTBI and 47 controls with no history of mTBI within the last 5 years. Participants were administered a simple symptom questionnaire, behavioral tests, and resting state EEG was measured using three frontopolar electrodes. An advanced machine learning algorithm called boosting was utilized to classify subjects into either injured or controls using power spectral densities on 1-min of resting EEG and the symptom questionnaire. RESULTS: Results based on leave-one-out cross-validation revealed that the addition of EEG measurements boosted the accuracy to approximately 91 ± 2% compared to 82 ± 4% from the symptom questionnaire alone. CONCLUSION: This study demonstrated the potential benefit of including EEG measurements to diagnose suspected brain injury patients. This is a step toward accurate and objective classification measurements that can be implemented on the field as a future injury assessment tool.

Evaluation of intraocular lens mechanical stability.

PURPOSE: To compare mechanical characteristics and stability of Clareon CNA0T0 intraocular lens (IOL) with 4 currently marketed monofocal IOLs and to evaluate axial displacement and simulated dioptric power shift using a range of compression diameters. SETTING: Alcon Laboratories, Inc., Fort Worth, Texas, USA. DESIGN: Experimental study. METHODS: Clareon CNA0T0, AcrySof SN60WF, enVista MX60, Tecnis ZCB00, and Vivinex iSert XY1 IOLs (10 per group) were assessed using standardized methods for axial displacement, optic decentration, and optic tilt per the International Organization for Standardization ISO11979-3. Axial displacement was also measured over a range of compression diameters (9.0 to 11.0 mm). RESULTS: At 10.0 mm compression, the mean axial displacement for the CNA0T0 IOL (0.02 mm ± 0.01 [SD]) was significantly lower than for the MX60, ZCB00, and XY1 IOLs (P < .005). At all compression diameters, the CNA0T0 and SN60WF IOLs had the lowest levels of axial displacement and corresponding simulated dioptric power shift at the corneal plane versus other IOL models. At 10.0 mm compression, the mean optic decentration was within ±0.06 mm for all models, and there were no significant differences between the CNA0T0 IOL and other IOLs. At 10.0 mm compression, the mean optic tilt was no greater than 1.2 degrees for all IOL models evaluated; however, the mean optic tilt for the CNA0T0 IOL was significantly lower than for the MX60 IOL (P < .005). CONCLUSION: The CNA0T0 and SN60WF IOLs showed the lowest levels of axial displacement and corresponding simulated dioptric power shift over all tested compression diameters, indicating they might provide the most consistent refractive outcomes.

Corneal Endothelial Cell Density and Morphology After Phacoemulsification in Patients With Primary Open-Angle Glaucoma and Cataracts: 2-Year Results of a Randomized Multicenter Trial.

PURPOSE: To evaluate corneal endothelial cell density (ECD) and morphology 2 years after phacoemulsification in subjects from the COMPASS trial (ClinicalTrials.gov, NCT01085357) who had mild-to-moderate primary open-angle glaucoma and visually significant cataracts. METHODS: The central corneal endothelium was evaluated by serial specular microscopy at 0 to 24 months. ECD, coefficient of variation, and percentage of hexagonal cells were evaluated by a central image analysis reading center and central corneal thickness (CCT) was evaluated by ultrasound pachymetry. RESULTS: Of 131 subjects who underwent routine phacoemulsification, analyzable endothelial images at 24 months were available for 126 subjects (96.2%). Mean ± SD central ECD at baseline was 2453 ± 359 cells/mm, decreasing by 10% ± 14% to 2195 ± 517 cells/mm at 3 months (P < 0.001) but stabilizing thereafter with mean endothelial cell loss (ECL) from baseline to 24 months of 9% ± 13% (P < 0.001). Twelve (9.5%) and 10 (7.9%) subjects experienced >30% ECL at 12 and 24 months, respectively. Neither coefficient of variation nor percentage of hexagonal cells changed significantly from baseline at any time point. Mean CCT was similar at baseline (550 ± 35 µm) and at 12 months (551 ± 37 µm) and 24 months (555 ± 35 µm). Age was significantly associated with ECL after cataract surgery (P = 0.02), but baseline intraocular pressure, number of glaucoma medications, and CCT were not. Similar results were observed in patients who underwent CyPass micro-stent implantation accompanying phacoemulsification. CONCLUSIONS: Phacoemulsification in eyes with mild-to-moderate primary open-angle glaucoma results in early ECL, with ECD stabilizing after 3 months and no effect on other endothelial stress markers up to 2 years postoperatively.

Patient-Reported Outcomes/Satisfaction and Spectacle Independence with Blended or Bilateral Multifocal Intraocular Lenses in Cataract Surgery.

PURPOSE: To compare patient-reported outcomes (PROs) and satisfaction results after multifocal intraocular lens (IOL) implantation in three groups: two receiving bilateral implantation of the same IOL and another undergoing blended vision with two different multifocal IOLs. PATIENTS AND METHODS: A questionnaire was administered to patients who had undergone uncomplicated cataract surgery and 2 months of follow-up: the first group underwent bilateral implantation with Alcon's AcrySof ReSTOR 3.0 lens ("3.0/3.0," n=78); the second group underwent implantation with the ReSTOR ActiveFocus 2.5 or the ReSTOR ActiveFocus 2.5 toric lens ("2.5 mini-monovision," n=102); and the third group underwent implantation with the ReSTOR 2.5 lens in the dominant eye and the ReSTOR 3.0 lens in the non-dominant eye ("2.5/3.0," n=89). RESULTS: Overall PROs and satisfaction was similar among the groups. Refractive outcomes and accuracy were similar among the groups, but the 2.5 mini-monovision group reported better intermediate vision. Refractive outcome differences were not meaningful among the groups and were not a differentiating factor in PROs. Substantially fewer patients in the 2.5 mini-monovision group noticed glare and halo compared with the 3.0/3.0 group (P<0.0001, chi-square test). No new safety concerns were reported. CONCLUSION: The 2.5 mini-monovision results in a higher percentage of patients being satisfied with intermediate vision than bilateral ReSTOR 3.0 or blended vision with ReSTOR 2.5/3.0 implants, but overall PRO differences were not statistically significant.