Hematopoietic Cell Transplantation after CD19 Chimeric Antigen Receptor T Cell-Induced Acute Lymphoblastic Lymphoma Remission Confers a Leukemia-Free Survival Advantage.

Consolidative hematopoietic cell transplantation (HCT) after CD19 chimeric antigen receptor (CAR) T cell therapy is frequently performed for patients with refractory/ relapsed B cell acute lymphoblastic leukemia (B-ALL). However, there is controversy regarding the role of HCT following remission attainment. We evaluated the effect of consolidative HCT on leukemia-free survival (LFS) in pediatric and young adult subjects following CD19 CAR T cell induced remission. We evaluated the effect of consolidative HCT on LFS in pediatric and young adult subjects treated with a 41BB-CD19 CAR T cell product on a phase 1/2 trial, Pediatric and Young Adult Leukemia Adoptive Therapy (PLAT)-02 (ClinicalTrials.gov identifier NCT02028455), using a time-dependent Cox proportional hazards statistical model. Fifty of 64 subjects enrolled in PLAT-02 phase 1 and early phase 2 were evaluated, excluding 14 subjects who did not achieve remission, relapsed, or died before day 63 post-CAR T cell therapy. An improved LFS (P = .01) was observed in subjects who underwent consolidative HCT after CAR T cell therapy versus watchful waiting. Consolidative HCT improved LFS specifically in subjects who had no prior history of HCT, with a trend toward significance (P = .09). This benefit was not evident when restricted to the cohort of 34 subjects with a history of prior HCT (P = .45). However, for subjects who had CAR T cell functional persistence of 63 days or less, inclusive of those with a history of prior HCT, HCT significantly improved LFS outcomes (P = .01). These data support the use of consolidative HCT following CD19 CAR T cell-induced remission for patients with no prior history of HCT and those with short functional CAR T cell persistence.

Evaluation of an Algorithm for Identifying Ocular Conditions in Electronic Health Record Data.

Importance: For research involving big data, researchers must accurately identify patients with ocular diseases or phenotypes of interest. Reliance on administrative billing codes alone for this purpose is limiting. Objective: To develop a method to accurately identify the presence or absence of ocular conditions of interest using electronic health record (EHR) data. Design, Setting, and Participants: This study is a retrospective analysis of the EHR data of patients (n = 122 339) in the Sight Outcomes Research Collaborative Ophthalmology Data Repository who received eye care at participating academic medical centers between August 1, 2012, and August 31, 2017. An algorithm that searches structured and unstructured (free-text) EHR data for conditions of interest was developed and then tested to determine how well it could detect the presence or absence of exfoliation syndrome (XFS). The algorithm was trained to search for evidence of XFS among a sample of patients with and without XFS (n = 200) by reviewing International Classification of Diseases, Ninth Revision or International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-9 or ICD-10) billing codes, the patient's problem list, and text within the ocular examination section and unstructured (free-text) data in the EHR. The likelihood that each patient had XFS was estimated using logistic least absolute shrinkage and selection operator (LASSO) regression. The EHR data of all patients were run through the algorithm to generate an XFS probability score for each patient. The algorithm was validated with review of EHRs by glaucoma specialists. Main Outcomes and Measures: Positive predictive value (PPV) and negative predictive value (NPV) of the algorithm were computed as the proportion of patients correctly classified with XFS or without XFS. Results: This study included 122 339 patients, with a mean (SD) age of 52.4 (25.1) years. Of these patients, 69 002 (56.4%) were female and 99 579 (81.4%) were white. The algorithm assigned a less than 10% probability of XFS for 121 085 patients (99.0%) as well as an XFS probability score of more than 75% for 543 patients (0.4%), more than 90% for 353 patients (0.3%), and more than 99% for 83 patients (0.07%). Validated by glaucoma specialists, the algorithm had a PPV of 95.0% (95% CI, 89.5%-97.7%) and an NPV of 100% (95% CI, 91.2%-100%). When there was ICD-9 or ICD-10 billing code documentation of XFS, in 86% or 96% of the records, respectively, evidence of XFS was also recorded elsewhere in the EHR. Conversely, when there was clinical examination or free-text evidence of XFS, it was documented with ICD-9 codes only approximately 40% of the time and even less often with ICD-10 codes. Conclusions and Relevance: The algorithm developed, tested, and validated in this study appears to be better at identifying the presence or absence of XFS in EHR data than the conventional approach of assessing only billing codes; such an algorithm may enhance the ability of investigators to use EHR data to study patients with ocular diseases.

The key informant strategy to determine the prevalence and causes of functional low vision among children in South India.

PURPOSE: To report the prevalence and causes of functional low vision (FLV) in school-age children in Coimbatore District, Tamil Nadu, India and to report our experience using the key informant (KI) method in this setting. METHODS: Children suspected of having low vision were identified by KIs or Aravind Eye Hospital personnel in Coimbatore District. All identified children underwent a cycloplegic refraction and full eye exam. A primary cause of decreased vision was determined for each child. The prevalence of FLV was calculated for children 6-14 years old. Spectacles and low vision devices were provided free of charge. RESULTS: 345 children aged 6-14 years were referred and 231 had FLV. The positive-predictive value of KI referrals was 64.5%. The prevalence of FLV was 0.071% (7.1 per 10,000; 95% CI 0.062-0.080%) and ranged from 0.026% to 0.141% across the district's blocks. Older children (age 11-14 years; OR 1.41; 95% CI 1.09-1.82) and males (OR 1.52; 95% CI 1.16-1.98) had greater odds of being diagnosed with FLV. The most common causes of FLV were retinal disorders (30.0%) and amblyopia (25.5%). Low vision devices were provided to 169 children who had a mean near and distance visual acuity improvement of 0.31 and 0.63 logMAR, respectively (p < 0.001). CONCLUSIONS: This study reports a moderate prevalence of FLV and demonstrates the ability of KIs to identify school-age children with FLV in South India. The provision of basic low vision services can improve visual outcomes in this population.

Does unbelted safety requirement affect protection for belted occupants?

OBJECTIVE: Federal regulations in the United States require vehicles to meet occupant performance requirements with unbelted test dummies. Removing the test requirements with unbelted occupants might encourage the deployment of seat belt interlocks and allow restraint optimization to focus on belted occupants. The objective of this study is to compare the performance of restraint systems optimized for belted-only occupants with those optimized for both belted and unbelted occupants using computer simulations and field crash data analyses. METHODS: In this study, 2 validated finite element (FE) vehicle/occupant models (a midsize sedan and a midsize SUV) were selected. Restraint design optimizations under standardized crash conditions (U.S.-NCAP and FMVSS 208) with and without unbelted requirements were conducted using Hybrid III (HIII) small female and midsize male anthropomorphic test devices (ATDs) in both vehicles on both driver and right front passenger positions. A total of 10 to 12 design parameters were varied in each optimization using a combination of response surface method (RSM) and genetic algorithm. To evaluate the field performance of restraints optimized with and without unbelted requirements, 55 frontal crash conditions covering a greater variety of crash types than those in the standardized crashes were selected. A total of 1,760 FE simulations were conducted for the field performance evaluation. Frontal crashes in the NASS-CDS database from 2002 to 2012 were used to develop injury risk curves and to provide the baseline performance of current restraint system and estimate the injury risk change by removing the unbelted requirement. RESULTS: Unbelted requirements do not affect the optimal seat belt and airbag design parameters in 3 out of 4 vehicle/occupant position conditions, except for the SUV passenger side. Overall, compared to the optimal designs with unbelted requirements, optimal designs without unbelted requirements generated the same or lower total injury risks for belted occupants depending on statistical methods used for the analysis, but they could also increase the total injury risks for unbelted occupants. CONCLUSIONS: This study demonstrated potential for reducing injury risks to belted occupants if the unbelted requirements are eliminated. Further investigations are necessary to confirm these findings.

How do drivers behave during indecision zone maneuvers?

Yellow signal indications at intersections are well-known to be a contributor to traffic crashes. This study examined drivers' behavior during yellow signal indication (i.e., indecision zone) maneuvers. Data from a driving simulator study was used, which included drivers' performance data when they encountered a yellow signal indication at intersections under different secondary-task conditions. This study calculated drivers' likelihood to go through a yellow signal indication and examined factors that are related to drivers' decision making on intersection traversing. The results showed that drivers' decision on stopping or not at a yellow signal indication was associated with different variables including age, distraction, pedal conditions, and time to stop line. Distracted drivers' insensitive behavior was also captured from the significant interaction effect between time to stop line and distraction conditions, which implied that intersection related crash risk may increase when drivers were distracted.

Factors affecting tether use and correct use in child restraint installations.

INTRODUCTION: Field studies show that top tethers go unused in half of forward-facing child restraint installations. METHOD: In this study, parent volunteers were asked to use the Lower Anchors and Tethers for Children (LATCH) to install child restraints in several vehicles to identify tether anchor characteristics that are associated with tether use. Thirty-seven volunteers were assigned to four groups. Each group tested two forward-facing child restraints in four of 16 vehicle models. Logistic regression models were used to identify predictors of tether use and correct use. RESULTS: Subjects used the tether in 89% of the 294 forward-facing child restraint installations and attached the tether correctly in 57% of the installations. Tethers were more likely to be used when the anchor was located on the rear deck as typically found in sedans compared with the seatback, floor, or roof. Tethers were less likely to be attached correctly when there was potentially confusing hardware present. No vehicle tether hardware characteristics or vehicle manual directions were associated specifically with correct tether routing and head restraint position. CONCLUSION: This study provides laboratory evidence that specific vehicle features are associated with tether use and correct use. PRACTICAL APPLICATIONS: Modifications to vehicles that make tether anchors easier to find and identify likely will result in increases in tether use and correct use.