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Quality of life in chronic kidney disease (CKD) is impaired by a large burden of symptoms including some that overlap with the symptoms of heart failure (HF). We studied a group of individual with CKD to understand the patterns and trajectories of HF-type symptoms in this setting.Prospective cohort study.3,044 participants in the Chronic Renal Insufficiency Cohort (CRIC) without prior diagnosis of HF.Sociodemographics, medical history, medications, vital signs, laboratory values, echocardiographic and EKG parameters.Trajectory over 5.5 years of a HF-type symptom score (modified Kansas City Cardiomyopathy Questionnaire [KCCQ] Overall Summary Score with a range of 0-100 where75 reflects clinically significant symptoms).Latent class mixed models were used to model trajectories. Multinomial logistic regression was used to model relationships of predictors with trajectory group membership.Five trajectories of KCCQ score were identified in the cohort of 3,044 adults, 45% of whom were female, and whose median age was 61 years. Group 1 (41.7%) had a stable high score (minimal symptoms, average score of 96); Groups 2 (35.6%) and 3 (15.6%) had stable but lower scores (mild symptoms, average 81, and clinically significant symptoms, average 52, respectively). Group 4 (4.9%) had a substantial worsening in symptoms over time (mean 31-point decline) and Group 5 (2.2%) had a substantial improvement (mean 33-point increase) in KCCQ score. A majority of Group 1 was male, non-diabetic, non-obese, and had higher baseline kidney function. A majority of Groups 2 and 3 had diabetes and obesity. A majority of Group 4 was male and had substantial proteinuria. Group 5 had the highest proportion of baseline cardiovascular disease (CVD).No validation cohort available, CKD management changes in recent years may alter trajectories, and latent class models depend on the missing at random assumption.Distinct HF-type symptom burden trajectories were identified in the setting of CKD, corresponding to different baseline characteristics. These results highlight the diversity of HF-type symptom experiences in individuals with CKD.

The aim of this study was to assess for distinct kidney function trajectories following left ventricular assist device (LVAD) placement. Cohort studies of LVAD recipients demonstrate that kidney function tends to increase early after LVAD placement, followed by decline and limited sustained improvement. Inter-individual differences in kidney function response may be obscured.We identified continuous flow LVAD implantations in US adults (2016-2017) from INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support). Primary outcomes were estimated glomerular filtration rate (eGFR) trajectories pre-implantation to ∼12 months. Latent class mixed models were applied to primary and validation samples. Clinical differences among trajectory groups were investigated.Among 4,615 LVAD implantations, 5 eGFR trajectory groups were identified. The 2 largest groups (Groups 1 and 2) made up80% of the cohort, and were similar to group average trajectories previously reported, with early eGFR rise followed by decline and stabilization. Three novel trajectory groups were found: worsening followed by sustained low kidney function (Group 3, 10.1%), sustained improvement (Group 4, 3.3%), and worsening followed by variation (Group 5, 1.7%). These groups differed in baseline characteristics and outcomes. Group 4 was younger and had more cardiogenic shock and pre-implantation dialysis; Group 3 had higher rates of pre-existing chronic kidney disease, along with older age.Novel eGFR trajectories were identified in a national cohort, possibly representing distinct cardiorenal processes. Type 1 cardiorenal syndrome may have been predominant in Group 4, and parenchymal kidney disease may have been predominant in Group 3.

Administering subsequent doses of rabies vaccine is not a medical emergency and does not require access to emergency department (ED) services. This study reviewed ED visits for rabies postexposure prophylaxis (PEP) to identify avoidable ED visits for subsequent rabies vaccination.This retrospective study included patients who received human rabies immune globulin (HRIG) or rabies vaccine at 15 EDs of a multi-hospital health system from 2016 to 2018. All ED visits were classified as initial or non-initial healthcare visits after animal exposure. Emergency department visits for non-initial healthcare were classified as necessary (HRIG administration, worsening symptoms, other emergent conditions, or vaccination during a natural disaster) or avoidable (rabies vaccination only).This study included 145 patients with 203 ED visits (113 initial and 90 non-initial healthcare visits). Avoidable ED visits were identified for 19% (28 of 145) of patients and 66% (59 of 90) of ED visits for non-initial healthcare. Contributing factors for avoidable ED visits were suboptimal ED discharge instructions to return to the ED for vaccination (n = 20 visits) and patients' inability to coordinate outpatient follow-up (n = 17 visits). Patients with previous avoidable ED visits had a 73% probability for unnecessarily returning to the ED for vaccination. The average number of avoidable ED visits observed per patient was 0.41 (95% CI = 0.25 to 0.56). Since the Centers for Disease Control and Prevention reports that 30,000 to 60,000 Americans initiates rabies PEP each year, we estimate that 7500 to 33,600 avoidable ED visits occur for rabies vaccination in the US each year.One of 5 patients who received rabies PEP in the ED had avoidable ED visits for subsequent rabies vaccination. This study highlights systemic lack of coordination following ED discharge and barriers to accessing rabies vaccine.

Aim The aim of this study was to describe the overall sleep quality, sleep patterns and severity of sleep difficulties among nursing faculty using the Pittsburgh Sleep Quality Index (PSQI). Design Cross‐sectional descriptive and correlational study. Methods A survey of faculty recruited from Texas Board of Nursing approved colleges/schools was used. A purposive, convenience sample of 105 faculty completed the PSQI, a reliable and valid instrument, in an online setting. Data was collected from January 2019 through April 2019. Results Nursing faculty reported sleep difficulty across all components, with more problems in sleep latency, sleep disturbances and subjective sleep quality. Overall, 70.5% of participants were reportedly “poor” sleepers, a salient finding. Faculty experienced poor sleep quality across all academic ranks and age groups. Sleep latency and subjective sleep quality were components that presented higher in severity for the youngest faculty.

SIGNIFICANCE. It is difficult to determine the most efficacious refractive correction for individuals with Down syndrome using routine clinical techniques. New objective methods that optimize spectacle corrections for this population may reduce limitations on daily living by improving visual quality. PURPOSE. This manuscript describes the methods and baseline characteristics of study participants in a National Eye Institute sponsored clinical trial to evaluate objectively derived spectacle corrections in adults with Down syndrome. Inter-session repeatability of the primary outcome measure (distance visual acuity) is also reported. METHODS. Adults with Down syndrome were enrolled into a 9 visit study to compare clinically derived spectacle corrections and two different objective spectacle corrections derived from wavefront aberration data. Spectacle corrections were randomized and dispensed for two months each. Distance visual acuity was measured with a Bailey-Lovie style chart. Inter-session repeatability of acuity was established by performing difference versus mean analysis from binocular acuity measures obtained through habitual corrections at visits 1 and 2.b RESULTS. Thirty adults (mean ± standard deviation age = 29 ± 10 years) with a large range of refractive errors were enrolled. Presenting visual acuity at visit 1 was reduced (right eye: 0.47 ± 0.20 logMAR, left eye: 0.42 ± 0.17 logMAR). The mean difference between visits 1 and 2 was 0.02 ± 0.06 logMAR with a coefficient of repeatability (1.96 x within subject standard deviation) of 0.12 logMAR. CONCLUSIONS. This study seeks to investigate new strategies to determine optical corrections that may reduce commonly observed visual deficits in individuals with Down syndrome. The good inter-session repeatability of acuity found in this study (6 letters) indicates that, despite the presence of reduced acuity, adults with Down syndrome performed the outcome measure for this clinical trial reliably.

OBJECTIVES: This analysis sought to determine factors (including adiposity-related factors) most associated with HF-type symptoms (fatigue, shortness of breath, and edema) in adults with chronic kidney disease (CKD). BACKGROUND: Symptom burden impairs quality of life in CKD, especially symptoms that overlap with HF. These symptoms are common regardless of clinical HF diagnosis, and may be affected by subtle cardiac dysfunction, kidney dysfunction, and other factors. We used machine learning to investigate cross-sectional relationships of clinical variables with symptom scores in a CKD cohort. METHODS: Participants in the Chronic Renal Insufficiency Cohort (CRIC) with a baseline modified Kansas City Cardiomyopathy Questionnaire (KCCQ) score were included, regardless of prior HF diagnosis. The primary outcome was Overall Summary Score as a continuous measure. Predictors were 99 clinical variables representing demographic, cardiac, kidney and other health dimensions. A correlation filter was applied. Random forest regression models were fitted. Variable importance scores and adjusted predicted outcomes are presented. RESULTS: The cohort included 3,426 individuals, 10.3% with prior HF diagnosis. BMI was the most important factor, with BMI 24.3 kg/m(2) associated with the least symptoms. Symptoms worsened with higher or lower BMIs, with a potentially clinically relevant 5 point score decline at 35.7 kg/m(2) and a 1-point decline at the threshold for low BMI, 18.5 kg/m(2). The most important cardiac and kidney factors were heart rate and eGFR, the 4(th) and 5(th) most important variables, respectively. Results were similar for secondary analyses. CONCLUSIONS: In a CKD cohort, BMI was the most important feature for explaining HF-type symptoms regardless of clinical HF diagnosis, identifying an important focus for symptom directed investigations.

SIGNIFICANCE Visual demands today incorporate a significant amount of time using digital devices. Results of this randomized crossover study of spherical and toric contact lenses demonstrated that participants were able to read smaller print size more comfortably and preferred toric contact lenses when using digital devices. PURPOSE The purpose of this study was to assess how toric contact lens correction affects subjective and objective outcomes of astigmatic patients using real-world digital devices. METHODS Adult participants, aged between 20 and 38 years with -0.75 to -1.50 D of astigmatism were enrolled in this double-masked randomized crossover 10-day study of Alcon Dailies Aqua Comfort Plus Sphere and Toric (Alcon, Geneva, Switzerland) contact lenses. Electronic high- and low-contrast near logMAR visual acuity and contrast sensitivity were tested. Reading performance was assessed using custom iPad applications; one used a reading sentences test, whereas the other analyzed zoom, contrast, and distance with website-based articles. Participants completed the Near Activity Visual Questionnaire and stated their preferred contact lens correction. RESULTS Thirty seven participants were screened, 35 participants were enrolled, and 34 participants completed the study. Toric lens correction improved near high- and low-contrast visual acuity by 0.5 to 1 full line (P < .0001) and allowed participants to read one line smaller text on the iPad (P = .01). Participants increased the zoom 11% (P = .004) and the contrast 4% (P = .006) more with spherical lenses while reading articles. Participants held the iPad at approximately the same distance, about 33 cm (P = .63). Eighty five percent of participants preferred the toric correction (P < .0001). Participants reported improved satisfaction with toric lens correction (P = .0002) and noticed the most benefit with tasks such as reading small print and labels/instructions. CONCLUSIONS This study used digital devices to demonstrate realistic benefits of toric contact lens designs for astigmatic patients.

• RATIONALE & OBJECTIVE: SPRINT compared the effect of intensive versus standard systolic blood pressure targets on cardiovascular morbidity and mortality. In this ancillary study, we evaluated the use of exploratory factor analysis (EFA) to combine biomarkers of kidney tubule health in urine and plasma and then study their role in longitudinal eGFR change and risk of acute kidney injury (AKI). • STUDY DESIGN: Observational cohort nested in a clinical trial. • SETTING & PARTICIPANTS: 2,351 SPRINT participants with eGFR < 60 ml/min/1.73m(2) at baseline. • EXPOSURE(S): Levels of neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), chitinase-3-like protein (YKL-40), kidney injury molecule-1 (KIM-1), monocyte chemoattractant protein-1 (MCP-1), alpha-1 microglobulin (α1m) and beta-2 microglobulin (β2m), uromodulin (UMOD), fibroblast growth factor-23 (FGF23), and intact parathyroid hormone (PTH). • OUTCOME(S): Longitudinal changes in eGFR and risk of AKI. • ANALYTICAL APPROACH: We performed EFA to capture different tubule pathophysiologic processes. We used linear mixed effects models to evaluate the association of each factor with longitudinal changes in eGFR. We evaluated the association of the tubular factors scores with AKI using Cox proportional hazards regression. • RESULTS: From ten biomarkers, EFA generated four factors reflecting tubule injury/repair (NGAL, IL-18 and YKL-40), tubule injury/fibrosis (KIM-1 and MCP-1), tubule reabsorption (α1m and β2m), and tubule reserve/mineral metabolism (UMOD, FGF23, and PTH). Each SD higher tubule reserve/mineral metabolism factor scores were associated with a 0.58% (0.39%, 0.67%) faster eGFR decline independent of baseline eGFR and albuminuria. Both the tubule injury/repair (HR per SD higher 1.18 [1.10, 1.37]) and tubule injury/fibrosis factors (HR 1.23 [1.02, 1.48]) were independently associated with future risk of AKI. • LIMITATIONS: The factors require validation in other settings. • CONCLUSIONS: EFA allows parsimonious subgrouping of biomarkers into factors which are differentially associated with progressive eGFR decline and AKI. These subgroups may provide insights into the pathological processes driving adverse kidney outcomes.

SIGNIFICANCE The challenges associated with clinical assessment of individuals with Down syndrome contribute to a wide range of estimates on the prevalence of keratoconus in the Down syndrome population. This work focuses on two topographical indices previously identified with keratoconus detection, applying them to a topographical data set meeting strict sampling criteria. PURPOSE The purpose of this study was to quantify the level of keratoconus-like topographical morphology in a large sample of eyes from individuals with Down syndrome, as identified by two keratoconus detection metrics: inferior-superior dioptric asymmetry (I-S) and KISA%. Severity of the asymmetry was also cast within the context of established Collaborative Longitudinal Evaluation of Keratoconus study disease severity classification criteria. METHODS Corneal topography data on both eyes of 140 subjects with Down syndrome and 138 control subjects were collected. Both I-S and KISA% were calculated from the topography data of eyes with sufficient sampling. Steep and flat keratometry data are reported for subjects with measurements on both eyes in the context of values recorded by the Collaborative Longitudinal Evaluation of Keratoconus study in frank keratoconus to examine within-eye and between-eye asymmetry and severity. RESULTS Keratoconus detection thresholds were exceeded in 20.8% of the eyes of subjects with Down syndrome and 2.2% of the eyes of controls using I-S and 11.8% of the eyes of subjects with Down syndrome and 0.0% of the eyes of controls using KISA%. Examination of the level of intraeye difference between flat and steep keratometry data for individuals with Down syndrome detected as having corneal morphology consistent with moderate keratoconus yields an average of 1.81 D of toricity, whereas the Collaborative Longitudinal Evaluation of Keratoconus study reported 3.28 D of toricity. CONCLUSIONS Morphology consistent with keratoconus as codified in the detection metrics I-S and KISA% is present in a large percentage of the eyes of individuals with Down syndrome. Differences were observed in the distribution of severity of corneal morphology in individuals with Down syndrome and the keratoconus population at large.

This study leverages advances in multivariate cross-classified random effects models to extend the Simple View of Reading to account for variation within readers and across texts, allowing for both the personalization of the reading function and the integration of the component skills and text and discourse frameworks for reading research. We illustrate the Complete View of Reading (CVR i) using data from an intensive longitudinal design study with a large sample of typical ( N = 648) and struggling readers ( N = 865) in middle school and using oral reading fluency as a proxy for comprehension. To illustrate the utility of the CVR i, we present a model with cross-classified random intercepts for students and passages and random slopes for growth, Lexile difficulty, and expository text type at the student level. We highlight differences between typical and struggling readers and differences across students in different grades. The model illustrates that readers develop differently and approach the reading task differently, showing differential impact of text features on their fluency. To be complete, a model of reading must be able to reflect this heterogeneity at the person and passage level, and the CVR i is a step in that direction. Implications for reading interventions and 21st century reading research in the era of “Big Data” and interest in phenotypic characterization are discussed.

Purpose Objective refraction based on wavefront aberration measures is a potential tool for patients unable to participate in a subjective refraction, but the selection of a single pupil diameter for determination of the objective refraction may pose challenges. The purpose of this study was to investigate the impact of pupil diameter on determination of objective refractions for adults with and without Down syndrome (DS) and predicted change in acuity with increasing pupil diameter. Methods Wavefront error was obtained from 27 adults with DS and 24 controls, and metric-optimized refractions were identified for 4- and 6-mm pupil diameters. Total dioptric difference between refractions for the two pupil sizes was calculated, and repeated measures analysis of variance was used to evaluate differences in refractions. Next, five control observers read acuity charts produced to simulate image quality of each subject if the same refraction was applied for both a 4- and 6-mm pupil diameter. A comparison of acuity with performance on a clear chart was used to calculate letters lost for each chart. Repeated measures analysis of variance was used to test for differences in letters lost from 4- and 6-mm diameters. Results The dioptric difference between refractions for 4- and 6-mm pupils was significantly greater in subjects with DS (0.51 diopters vs. 0.19 diopters, P = 0.0012). Letters lost for predicted acuity was less for the 4-mm diameter than 6 mm for charts representing DS eyes (6.5 letters vs. 11 letters, P < 0.0001), as well as for typical eyes (4.5 letters vs. 8 letters, P < 0.0001). Conclusions Differences between refractions by pupil diameter were similar to the repeatability of subjective refraction. Visual acuity differences were clinically small, suggesting similar performance for objective refractions with increasing pupil diameter. Translational Relevance This work quantifies the potential impact of pupil diameter change on the performance of wavefront optimized refractions in clinical patients.

Ocular hypertension is a causal risk-factor to developing glaucoma. This is associated with stiffening of the trabecular meshwork (TM), the primary site of resistance to aqueous-humor-outflow. The mechanisms underlying this stiffening or how pathologic extracellular matrix (ECM) affects cell function are poorly understood. It is recognized that mechanotransduction systems allow cells to sense and translate the intrinsic biophysical properties of ECM into intracellular signals to control gene transcription, protein expression, and cell behavior. Using an anterior segment perfusion model, we document that there are significantly more low flow regions that are much stiffer, and fewer high flow regions that are less stiff in glaucomatous TM (GTM) when compared to non-glaucomatous TMs (NTM). GTM tissue also has fewer cells overall when compared with NTM tissue. In order to study the role of pathologic ECM in glaucoma disease progression, we conducted studies using cell derived matrices (CDM). First, we characterized the mechanics, composition and organization of fibronectin in ECM deposited by GTM and NTM cells treated with glucocorticosteroids. Then, we determined that these GTM-derived ECM are able to induce stiffening of normal NTM cells, and alter their gene/protein expression to resemble that of a glaucomatous phenotype. Further, we demonstrate that GTM-derived ECM causes endoplasmic reticular stress in NTM. They also became resistant to being reorganized by these NTM cells. These phenomena were exacerbated by ECMs obtained from steroid treated glaucoma model groups. Collectively, our data demonstrates that CDMs represent a novel tool for the study of bidirectional interactions between TM cells and their immediate microenvironment. Statement of Significance Extracellular matrix (ECM) changes are prevalent in a number of diseases. The precise mechanisms by which changes in the ECM contribute to disease progression is unclear, primarily due to absence of appropriate models. Here, using glaucoma as a disease model, we document changes in cell derived matrix (CDM) and tissue mechanics that contribute to the pathology. Subsequently, we determine the effect that ECMs from diseased and healthy individuals have on healthy cell behaviors. Data emanating from this study demonstrate that CDMs are a potent tool for the study of cell-ECM interactions.

SIGNIFICANCE: These results demonstrate that accommodation in children is more accurate and less variable when performing a sustained near task with increased cognitive demand. Additionally, children with increased uncorrected hyperopia have less stable accommodative responses, which may have visual implications during sustained near tasks. PURPOSE: This study investigated accommodative accuracy (lag) and variability during sustained viewing for passive and active tasks in children and adults with emmetropia and uncorrected hyperopia. METHODS: Lag and variability (root mean square [RMS] and low-frequency component) were measured in 54 children aged 3 to 0.05), but low-frequency component was larger during passive viewing (P=0.04). Group 1 had significantly higher RMS and low-frequency component than Group 2 and the adults in the passive condition and greater low-frequency component in the active condition. In children, hyperopia was independently associated with RMS and low-frequency component under passive (RMS 95% CI: 0.04–0.15, low-frequency component 95% CI: 0.00011–0.00065) and active (RMS 95% CI: 0.001–0.06, 95% CI: 0.000014–0.00023) viewing. CONCLUSIONS: Accommodation is more accurate and less variable when children are engaged in the task. Children also have more variable accommodation than adults. Additionally, children with greater hyperopia have more variable accommodation during sustained near tasks.

Studies using questionnaires report that COVID-19 restrictions resulted in children spending significantly less time outdoors. This study used objective measures to assess the impact of pandemic-related restrictions on children’s behavior. A total of 19 healthy 8–12-year-old boys were observed before and during social restriction periods. Of these, 11 boys were reassessed after restrictions were lifted. For each session, Actiwatches were dispensed for measures of time outdoors, activity, and sleep. Changes overall and by school status were assessed using signed-rank test and Wilcoxon rank sum tests. During restrictions, children spent significantly less time outdoors (p = 0.001), were less active (p = 0.001), and spent less time engaged in moderate-to-vigorous physical activity (p = 0.004). Sleep duration was not significantly different between sessions (p &gt, 0.99), but bedtime and wake time shifted to a later time during restrictions (p &lt, 0.05 for both). Time outdoors and activity returned close to pre-pandemic levels after restrictions were lifted (p &gt, 0.05 for both). Children’s behaviors significantly changed during the COVID-19 pandemic. The reduction in outdoor light exposure is of importance due to the role of light in the etiology of myopia and vitamin D production. The reduction in physical activity may have negative health effects in terms of obesity and depression, although further research is required to ascertain the long-term effects.

Down syndrome (DS) is associated with ocular and cognitive sequelae, which both have the potential to influence clinical measures of refractive error. This study compares variability of autorefraction among subjects with and without DS. Grand Seiko autorefraction was performed on 139 subjects with DS (age: 8–55, mean: 25 ± 9 yrs) and 138 controls (age: 7–59, mean: 25 ± 10 yrs). Subjects with three refraction measures per eye (DS: 113, control: 136) were included for analysis. Each refraction was converted to power vector notation (M, J0, J45) and a difference in each component (ΔM, ΔJ0, ΔJ45) was calculated for each refraction pairing. From these quantities, average dioptric strength ( JOURNAL/opvis/04.02/00006324-201705000-00005/math_5MM1/v/2017-07-27T051618Z/r/image-tiff : square root of the sum of the squares of M, J0, and J45) and average dioptric difference ( JOURNAL/opvis/04.02/00006324-201705000-00005/math_5MM2/v/2017-07-27T051618Z/r/image-tiff : square root of the sum of the squares of ΔM, ΔJ0, and ΔJ45) were calculated. The DS group exhibited a greater median JOURNAL/opvis/04.02/00006324-201705000-00005/math_5MM3/v/2017-07-27T051618Z/r/image-tiff (1Q: 1.38D M: 2.38D 3Q: 3.41D) than control eyes (1Q: 0.47D M: 0.96D 3Q: 2.75D) (P < .001). Likewise, the DS group exhibited a greater median JOURNAL/opvis/04.02/00006324-201705000-00005/math_5MM4/v/2017-07-27T051618Z/r/image-tiff in refraction (1Q: 0.27D M: 0.42D 3Q: 0.78D) than control eyes (1Q: 0.11D M: 0.15D 3Q: 0.23D) (P < .001) with 97.1% of control eyes exhibiting JOURNAL/opvis/04.02/00006324-201705000-00005/math_5MM5/v/2017-07-27T051618Z/r/image-tiff ≤0.50D, compared to 59.3% of DS eyes. An effect of JOURNAL/opvis/04.02/00006324-201705000-00005/math_5MM6/v/2017-07-27T051618Z/r/image-tiff on JOURNAL/opvis/04.02/00006324-201705000-00005/math_5MM7/v/2017-07-27T051618Z/r/image-tiff was not detected (P = .3009) nor was a significant interaction between JOURNAL/opvis/04.02/00006324-201705000-00005/math_5MM8/v/2017-07-27T051618Z/r/image-tiff and group detected (P = .49). In the current study, comparing three autorefraction readings, median total dioptric difference with autorefraction in DS was 2.8 times the levels observed in controls, indicating greater potential uncertainty in objective measures of refraction for this population. The analysis demonstrates that J45 is highly contributory to the observed variability.

The purpose of this study was to examine psychological, substance use, and sociodemographic predictors of 12-month suicide ideation and attempts across six US racial/ethnic groups-white, Latino/a, Black, Asian or Pacific Islander (A/PI), American Indian or Alaska Native (AI/AN), and multiracial adults. Multiple logistic regression analyses were conducted for 218,765 adults who participated in the 2008-2013 National Survey on Drug Use and Health. Overall, commonly cited factors were associated with increased risk for suicide ideation and attempt for some racial/ethnic groups, but not for others. As one example, 12-month depression was associated with 12-month suicide attempt for A/PI, AI/AN, Latino/a, and white, but not for Black or multiracial adults. Alcohol abuse and dependence were also associated with suicide attempt for AI/AN, Black, and white respondents but not for other racial/ethnic groups. Risk factors for suicide ideation and attempt may not increase risk universally. More theoretically supported research is needed.

Purpose This study aimed to quantify the impact of blur, contrast, and ghosting on perceived overall image quality (IQ) as well as resultant predicted visual acuity, utilizing simulated acuity charts from objective refraction among eyes of individuals with Down syndrome (DS). Methods Acuity charts were produced, simulating the retinal image when applying 16 different metric-derived sphero-cylindrical refractions for each eye of 30 adult patients with DS. Fourteen dilated adult observers (normal vision) viewed subsets of logMAR acuity charts displayed on an LCD monitor monocularly through a unit magnification 3-mm aperture telescope. Observers rated features blur, ghosting, and contrast on 10-point scales (10 = poorest) and overall IQ on a 0- to 100-point scale (100 = best) and read each chart until five total letters were missed (logMAR technique). Mixed modeling was used to estimate feature influence on overall perceived IQ and relative acuity (compared with an unaberrated chart), separately. Results Perceived IQ spanned the entire scale (mean = 59 ± 22) and average reduction in relative acuity was two lines (0.2 ± 0.14 logMAR). Perceived blur, ghosting, and contrast were individually correlated with overall IQ and relative acuity. Blur, contrast, and ghosting exert unique effects on overall perceived IQ (P < 0.05). Blur (b = -.009, P < 0.001) and ghosting (b = -.003, P < 0.001) influence relative acuity over and beyond their effects on overall IQ (b = .001, P < 0.0001) and contrast. Conclusions Objectively identified refractions would ideally provide high contrast, low blur, and low ghosting. These data suggest that blur and ghosting may be given priority over contrast when improving acuity is the goal. Translational Relevance Findings may guide objective refraction in clinical care.

The original unstructured Glasgow Outcome Scale (uGOS) and the newer structured interviews GOS and the Extended GOS (GOS-E) have been used widely as outcomes in severe traumatic brain injury (TBI) trials. We compared outcome categories (ranging from dead [D] to good recovery [GR]) for each measure in a randomized trial of transfusion threshold and the implications of measure choice and analysis methods for the results of the trial. We planned to explore patient symptomology possibly driving any discrepancies between the patient's uGOS and GOS scores. Category correspondence between uGOS and GOS scores occurred in 160 (88.4%) of the 181 analyzed cases. The GOS-E and GOS instruments incorporated more behavioral/cognitive/social and other components, leading to a worse outcome in some cases than for the uGOS. Choice of outcome measure and analysis led to incongruous conclusions. Dichotomizing uGOS into favorable outcome (GR and moderate disability [MD] categories) versus unfavorable (severe disability [SD], vegetative state [VS], and D categories), we observed a significant effect of transfusion threshold (odds ratio [OR] = 0.51, p = 0.03; adjusted OR = 0.40, p = 0.02). For the same dichotomization of GOS and GOS-E, the effect was not statistically significant but the ORs were similar (ORs between 0.57 and 0.68, p > 0.15 for all). An effect was not detected using ordinal logistic regression or sliding dichotomy method for all three measures. Differences in categorizations of subjects between moderate and severe disability among the scales impacted conclusions of the trial. In future studies, particular attention should be given to implementing GOS measures and describing the methodology for how outcomes were ascertained.

Objectives:Long-term neurological response to treatment after a severe traumatic brain injury (sTBI) is a dynamic process. Failure to capture individual heterogeneity in recovery may impact findings from single endpoint sTBI randomized controlled trials (RCT). The present study re-examined the efficacy of erythropoietin (Epo) and transfusion thresholds through longitudinal modeling of sTBI recovery as measured by the Disability Rating Scale (DRS). This study complements the report of primary outcomes in the Epo sTBI RCT, which failed to detect significant effects of acute treatment at 6 months post-injury.Methods:We implemented mixed effects models to characterize the recovery time-course and to examine treatment efficacy as a function of time post-injury and injury severity.Results:The inter-quartile range (25th–75thpercentile) of DRS scores was 20–28 at week1; 8–24 at week 4; and 3–17 at 6 months. TBI severity group was found to significantly interact with Epo randomization group on mean DRS recovery curves. No significant differences in DRS recovery were found in transfusion threshold groups.Conclusions:This study demonstrated the value of taking a comprehensive view of recovery from sTBI in the Epo RCT as a temporally dynamic process that is shaped by both treatment and injury severity, and highlights the importance of the timing of primary outcome measurement. Effects of Epo treatment varied as a function of injury severity and time. Future studies are warranted to understand the possible moderating influence of injury severity on treatment effects pertaining to sTBI recovery. (JINS, 2019,25, 293–301)

Understanding the dynamic disease process is vital in early detection, diagnosis, and measuring progression. Continuous-time Markov chain (CTMC) methods have been used to estimate state-change intensities but challenges arise when stages are potentially misclassified. We present an analytical likelihood approach where the hidden state is modeled as a three-state CTMC model allowing for some observed states to be possibly misclassified. Covariate effects of the hidden process and misclassification probabilities of the hidden state are estimated without information from a 'gold standard' as comparison. Parameter estimates are obtained using a modified expectation-maximization (EM) algorithm, and identifiability of CTMC estimation is addressed. Simulation studies and an application studying Alzheimer's disease caregiver stress-levels are presented. The method was highly sensitive to detecting true misclassification and did not falsely identify error in the absence of misclassification. In conclusion, we have developed a robust longitudinal method for analyzing categorical outcome data when classification of disease severity stage is uncertain and the purpose is to study the process' transition behavior without a gold standard.

BACKGROUND The effect of red blood cell (RBC) storage on oxygenation in critically ill patients is still unknown. The objective of this study was to determine the association of RBC storage with oxygenation, long-term neurologic recovery, and death after traumatic brain injury. METHODS We used data from a 2 × 2 factorial randomized controlled trial of administration of erythropoietin or placebo and of assignment to transfusion threshold of less than 7g/dL or less than 10 g/dL in neurosurgical intensive care units in two US Level 1 trauma centers. Patients had severe traumatic brain injury with closed head injury, were unable to follow commands, and were enrolled within 6 hours of injury. Blood oxygenation 1 hour after the transfusion as measured by jugular venous oxygen saturation (n = 59) was the primary outcome. Secondary outcomes were brain tissue oxygenation (n = 77), 6-month Glasgow Outcome Scale (GOS) score (n = 122) collected using a structured interview and dichotomized into favorable (good recovery or moderate disability) or unfavorable outcome (severe disability, vegetative state, or dead), and mortality (n = 125). RBC age was defined as the maximum age of RBCs over all units in one transfusion per patient. For long-term outcomes, RBC age was defined as the mean age over all units given. RESULTS We failed to detect an association of RBC age with jugular venous oxygen saturation (linear regression β = 1.59; 95% confidence interval [CI], -2.99 to 6.18; p = 0.49), brain tissue oxygenation (linear regression β = 0.20; 95% CI, -0.23 to 0.63; p = 0.36), GOS score (odds ratio, 1.37; 95% CI, 0.53-3.57; p = 0.52), and mortality (hazard ratio, 1.35; 95% CI, 0.61-2.98; p = 0.46). CONCLUSION Limitations of this study include the fact that the RBC ages were not randomized, although this was a prospective study. We conclude that older blood does not seem to have adverse effects in severe traumatic brain injury. LEVEL OF EVIDENCE Prognostic study, level III.

Understanding Alzheimer’s disease (AD) dynamics is essential in diagnosis and measuring progression for clinical decision-making; however, clinical instruments are imperfect at classifying true disease stages. This research evaluates sensitivity and determinants of AD stage changes longitudinally using current classifications of “mild,” “moderate,” and “severe” AD, using Mini-Mental State Examination (MMSE), Alzheimer’s Disease Assessment Scale–Cognitive subscale (ADAS-Cog), and the Clinical Dementia Rating–Sum of Boxes (CDR-SB) thresholds. Age and pre-progression rate were significant determinants of AD progression using MMSE alone to stage AD, and pre-progression was found to impact disease progression with CDR-SB. Sensitivity of these instruments for identifying clinical stages of AD to correctly staging a “moderate” level of disease severity for outcomes MMSE, CDR-SB, and ADAS-Cog was 92%, 78%, and 92%, respectively. This research derives longitudinal sensitivity of clinical instruments used to stage AD useful for clinical decision-making. The MMSE and ADAS-Cog provided adequate sensitivity to classify AD stages.

Observers with central field loss typically fixate within a non-foveal region called the preferred retinal locus, which can include localized sensitivity losses, or micro-scotomas (Krishnan and Bedell, 2018). In this study, we simulated micro-scotomas at the fovea and in the peripheral retina to assess their impact on reading speed. Ten younger (50 years old) naïve observers with normal vision monocularly read high and/or low contrast sentences, presented at or above the critical print size for young observers at the fovea and at 5 and 10 deg in the inferior visual field. Reading material comprised MNREAD sentences and sentences taken from novels that were presented in rapid serial visual presentation (RSVP) format. Randomly distributed 13 × 13 arc min blocks corresponding to 0 – 78% of the text area (corresponding to ~0 – 17 micro-scotomas/deg(2)) were set to the background luminance to simulate micro-scotomas. A staircase algorithm estimated maximum reading speed from the threshold exposure duration for each combination of retinal eccentricity, contrast and micro-scotoma density in both age groups. Log(10)(RSVP reading speed) decreased significantly with simulated micro-scotoma density and eccentricity. Across conditions, reading speed was slower with low- compared to high-contrast text and was faster in younger than older normal observers. For a given eccentricity and contrast, a higher density of random element losses maximally affected older observers with normal vision. These outcomes may explain some of the reading deficits observed in older observers with central field loss.

SIGNIFICANCE Significant differences in light exposure were observed between school and summer in children, whereas activity and sleep were similar. Associations between parent and child behaviors suggest a potential mechanism for how myopia is transmitted from parents to children through patterns of environmental exposure, in addition to genetic factors. PURPOSE Objectively measured time outdoors, light exposure, activity, and sleep were examined in children during school and summer and assessed with eye growth. Associations between parent and child behaviors were evaluated. METHODS Children (aged 7.6 ± 1.8 years, n = 60) in Houston, TX, wore an actigraph device for three 2-week sessions (fall school, spring school, summer) to quantify time outdoors, light exposure, activity, and sleep. Cycloplegic autorefraction (WAM-5500; Grand-Seiko, Tokyo, Japan) and axial length (LenStar; Haag-Streit AG, Koeniz, Switzerland) were measured at baseline and 1 year. A subset of parents wore the device during their child's first 2-week session to compare behaviors (n = 33). RESULTS Children spent 94.4 ± 30.6 minutes per day outdoors in spring, 110.6 ± 45.7 minutes in summer, and 72.2 ± 31.0 minutes in fall, with significant differences between sessions (P < .0001). Daily activity and sleep duration were similar across sessions (P = .73 and .06, respectively). Axial growth rate decreased with light exposure, but did not reach significance after adjusting for baseline axial length, age, sex, activity, and parental myopia (P = .073). Parent and child time outdoors and sleep duration were significantly correlated (P = .0002 and 0.026, respectively). CONCLUSIONS Significant differences in light exposure were observed between school and summer, whereas activity and sleep were constant throughout the year. Children's behaviors were associated with their parent's behaviors, which may represent a modifiable component to potential environmental influences on eye growth. However, light exposure was not a significant environmental influence on axial growth in this study.

SIGNIFICANCE Our results demonstrate that blur detection thresholds are elevated in young children compared with adults, and poorer blur detection thresholds are significantly correlated with the magnitude of accommodative microfluctuations. Given that accommodative microfluctuations are greater with greater accommodative responses, these findings may have implications for young uncorrected hyperopes. PURPOSE This study investigated the association between subjective blur detection thresholds and accommodative microfluctuations in children 3 years to younger than 10 years old and adults. METHODS Blur detection thresholds were determined in 49 children with habitually uncorrected refractive error (+0.06 to +4.91 diopters [D] spherical equivalent) and 10 habitually uncorrected adults (+0.08 to +1.51 D spherical equivalent) using a custom blur chart with 1° sized optotypes at 33 cm. Letters were blurred by convolution using a Gaussian kernel (SDs of 0.71 to 11.31 arc minutes in √2 steps). Subjective depth of field was determined in subjects 6 years or older and adults. Accommodative microfluctuations, pupils, and lag were measured using infrared photorefraction (25 Hz). RESULTS Children had greater blur detection thresholds (P < .001), accommodative microfluctuations (P = .001), and depth of field (P < .001) than adults. In children, increased blur detection thresholds were associated with increased accommodative microfluctuations (P < .001), increased uncorrected hyperopia (P = .01), decreased age (P < .001), and decreased pupil size (P = .01). In a multiple linear regression analysis, blur detection thresholds were associated with accommodative microfluctuations (P < .001) and age (P < .001). Increased accommodative microfluctuations were associated with increased uncorrected hyperopia (P = .004) and decreased pupil size (P = .003) and independently associated with uncorrected hyperopia (P = .001) and pupil size (P = .003) when controlling for age and lag. CONCLUSIONS Children did not have adult-like blur detection thresholds or depth of field. Increased accommodative microfluctuations and decreased age were independently associated with greater blur detection thresholds in children 3 years to younger than 10 years. Larger amounts of uncorrected hyperopia in children appear to increase blur detection thresholds because the greater accommodative demand and resulting response increase accommodative microfluctuations.

PURPOSE Individuals with Down syndrome may experience greater difficulty reliably performing visual acuity (VA) tests because of intellectual disability and limitations in visual quality. This study evaluated the repeatability of acuity (Bailey-Lovie [BL] and HOTV) in subjects with and without Down syndrome. METHODS High-contrast VA was measured in both eyes of 30 subjects with Down syndrome (mean, 30 years; range, 18 to 50 years) and 24 control subjects without Down syndrome (mean, 29 years; range, 18 to 50 years). In the Down syndrome group, 23 subjects performed BL, and 7 subjects performed HOTV. All control subjects performed both BL and HOTV, but for HOTV analysis, only seven age-matched control subjects were included. For each eye, subjects performed VA three times on different charts (computer controlled, single-line display) until five total letters were missed on each chart. A repeated-measure ANOVA was used to compare the acuity measures between groups. RESULTS The average logMAR VA for subjects with Down syndrome was approximately six lines worse than the control subjects (BL: Down syndrome = right eye: 0.51 ± 0.16, left eye: 0.53 ± 0.18; control = right eye: -0.06 ± 0.06, left eye: -0.06 ± 0.08, P < .0001; HOTV: Down syndrome = right eye: 0.47 ± 0.19, left eye: 0.46 ± 0.16; control: right eye = -0.11 ± 0.09, left eye: -0.07 ± 0.07, P < .001). Bailey-Lovie VA repeatability (1.96 * Sw * √2) was 0.13 logMAR (6.5 letters) for Down syndrome and 0.09 logMAR (4.5 letters) for control subjects. HOTV VA repeatability was 0.16 logMAR (eight letters) for both Down syndrome and control subjects. CONCLUSIONS Despite poorer acuity in individuals with Down syndrome, repeatability of VA measurements was comparable to control subjects for both BL and HOTV techniques.

Parameter dependency within data sets in simulation studies is common, especially in models such as Continuous-Time Markov Chains (CTMC). Additionally, the literature lacks a comprehensive examination of estimation performance for the likelihood-based general multi-state CTMC. Among studies attempting to assess the estimation, none have accounted for dependency among parameter estimates. The purpose of this research is twofold: 1) to develop a multivariate approach for assessing accuracy and precision for simulation studies 2) to add to the literature a comprehensive examination of the estimation of a general 3-state CTMC model. Simulation studies are conducted to analyze longitudinal data with a trinomial outcome using a CTMC with and without covariates. Measures of performance including bias, component-wise coverage probabilities, and joint coverage probabilities are calculated. An application is presented using Alzheimer’s disease caregiver stress levels. Comparisons of joint and component-wise parameter estimates yield conflicting inferential results in simulations from models with and without covariates. In conclusion, caution should be taken when conducting simulation studies aiming to assess performance and choice of inference should properly reflect the purpose of the simulation.

PURPOSE Peripheral retinal defocus has been implicated in myopia progression. The effect of commercially available spherical soft contact lenses (SCLs) on peripheral defocus of adult myopic eyes was investigated. METHODS Twenty-five young adults with spherical equivalent (SE) refractions between -0.50D and -6.00D were enrolled. Cycloplegic autorefraction (right eye) was measured centrally and ±20°, ±30°, and ±40° from the line of sight along the horizontal meridian using an autorefractor. Four commercially available spherical SCLs (Biofinity, Acuvue2, PureVision2, and Air Optix Night & Day Aqua) were evaluated. SE defocus (M) was used to calculate relative peripheral defocus (RPD) while wearing each SCL and relative peripheral refraction of the uncorrected eye. Spherical aberration (SA) changes caused by each SCL were measured along the line of sight by aberrometry. Peripheral defocus was analyzed using repeated-measures analyses of variance (RM-ANOVA). The association between changes in axial SA and the change in peripheral defocus was evaluated using linear mixed models. RESULTS The mean age (±SD) and central SE refractive error were 24.0 ± 1.3 years and -3.45 ± 1.42D, respectively. PureVision2 did not change RPD (P = .33). Significant myopic shifts on the temporal retina were found with three lenses: Acuvue 2 (-0.29D at 30°; -0.80D at 40°; both P ≤ .01), Biofinity (-1.21 D at 40°; P = .02), and Air Optix Night & Day Aqua (-0.23D at 20°, -0.48D at 30°, and -1.50D at 40°; all P < .004). All SCLs caused a negative change in SA. SCLs inducing less negative (more positive) SA changes were associated with a less hyperopic change in RPD. CONCLUSIONS Spherical SCL design can influence the peripheral defocus profile experienced by a myopic eye. Several, but not all, SCLs reduced peripheral hyperopia. Differences in how SCL types influence peripheral defocus may have implications for myopia progression.

Research on educator stress and its effects on health outcomes faces numerous methodological challenges that affect the design, execution and analysis of scientific investigations. The chapter begins with an overview of the statistical challenges associated with multilevel field studies, which are ubiquitous in research on educator stress. Secondly, we will examine the specific challenges posed by time in the study of stress and the various methods and models used to capture the many roles of time in stress research, including individualized developmental and dynamic models, and ecological momentary assessment (EMA). Finally, we conclude with an examination of the special challenges that arise in the study of event occurrence in multilevel settings, such as leaving the workforce, changing employers, or experiencing a medical incident. These challenges stem from the complex nature of the construct of stress, the time frame over which stress exerts its influences on behavior, health and emotional well-being the many levels at which occupational settings create and mitigate stress, and the many levels at which individuals experience stress and demonstrate its influence on health and work outcomes. The chapter provides an overview of some of the more salient methodological, measurement, and analysis related issues that affect the work reported on in this volume. Our goal is to provide the reader with a firm understanding of the more complex methods and analyses relevant to the study of educator stress in an effort to strengthen the readers’ ability to benefit from the science presented throughout the volume.

Purpose To assess the repeatability of simulated keratometry measures obtained with Zeiss Atlas topography for subjects with and without Down syndrome (DS). Methods Corneal topography was attempted on 140 subjects with DS and 138 controls (aged 7-59 years). Subjects who had at least three measures in each eye were included in analysis (DS: n = 140 eyes (70 subjects) and controls: n = 264 eyes (132 subjects)). For each measurement, the steep corneal power (K), corneal astigmatism, flat K orientation, power vector representation of astigmatism (J0, J45), and astigmatic dioptric difference were determined for each measurement (collectively termed keratometry values here). For flat K orientation comparisons, only eyes with >0.50 DC of astigmatism were included (DS: n = 131 eyes (68 subjects) and control: n = 217 eyes (119 subjects)). Repeatability was assessed using (1) group mean variability (average standard deviation (SD) across subjects), (2) coefficient of repeatability (COR), (3) coefficient of variation (COV), and (4) intraclass correlation coefficient (ICC). Results The keratometry values showed good repeatability as evidenced by low group mean variability for DS versus control eyes (≤0.26D vs. ≤0.09D for all dioptric values; 4.51° vs. 3.16° for flat K orientation); however, the group mean variability was significantly higher in DS eyes than control eyes for all parameters (p ≤ 0.03). On average, group mean variability was 2.5 times greater in the DS eyes compared to control eyes across the keratometry values. Other metrics of repeatability also indicated good repeatability for both populations for each keratometry value, although repeatability was always better in the control eyes. Conclusions DS eyes showed more variability (on average: 2.5×) compared to controls for all keratometry values. Although differences were statistically significant, on average 91% of DS eyes had variability ≤0.50D for steep K and astigmatism, and 75% of DS eyes had variability ≤5 degrees for flat K orientation.

Purpose To determine which optimized image quality metric (IQM) refractions provide the best predicted visual acuity (VA). Methods Autorefraction (AR), habitual refraction (spectacles, n = 23; unaided, n = 7), and dilated wavefront error (WFE) were obtained from 30 subjects with Down syndrome (DS; mean age, 30 years; range, 18–50). For each eye, the resultant metric value for 16 IQMs was calculated after >25000 sphero-cylindrical combinations of refraction were added to the measured WFE to generate residual WFE. The single refraction corresponding to each of the 16 optimized IQMs per eye was selected and used to generate acuity charts. Charts also were created for AR, habitual refraction, and a theoretical zeroing of all lower-order aberrations, and grouped into 10 sets with a clear chart in each set. Dilated controls (five observers per set) read each chart until five letters were missed on a high contrast monitor through a unit magnification telescope with a 3 mm pupil aperture. Average letters lost for the five observers for each chart was used to rank the IQMs for each DS eye. Results Average acuity for the best performing refraction for all DS eyes was within five letters (0.11 ± 0.05 logMAR) of the clear chart acuity. Optimized IQM refractions had ∼3.5 lines mean improvement from the habitual refraction (0.37 ± 0.22 logMAR, P < 0.001). Three metrics (Visual Strehl Ratio [VSX], VSX computed in frequency domain [VSMTF], and standard deviation of intensity values [STD]) identified refractions that were ranked first, or within 0.09 logMAR of first, in >98% of the eyes. Conclusions Optimized IQM refraction is predicted to improve VA in DS eyes based on control observers reading simulated charts. Translational Relevance Refractions identified through optimization of IQM may bypass some of the challenges of current refraction techniques for patients with DS. The optimized refractions are predicted to provide better VA compared to their habitual correction.

Patients with severe traumatic brain injury (TBI) are at risk of the development of acute respiratory distress syndrome (ARDS). TBI and ARDS pathophysiologic mechanisms are known to independently involve significant inflammatory responses. The literature on the association between plasma inflammatory cytokines and ARDS in patients with TBI is sparse. The study was a secondary analysis of the safety of a randomized trial of erythropoietin and transfusion threshold in patients with severe TBI. Inflammatory markers within the first 24 hours after injury were compared in patients who developed ARDS and patients without ARDS, using Cox proportional hazards models. There were 200 patients enrolled in the study. The majority of plasma and cerebrospinal fluid (CSF) cytokine levels were obtained within 6 hours. Plasma proinflammatory markers IL-6 and IL-8 and anti-inflammatory marker IL-10 were associated with the development of ARDS (adjusted hazard ratio (HR) = 1.55, confidence interval (CI) = 1.14, 2.11, P = 0.005 for IL-6; adjusted HR = 1.32, CI = 1.10, 1.59, P = 0.003 for IL-8). Plasma markers of IL-6, IL-8, and IL-10 are associated with ARDS in patients with severe TBI. NCT00313716 registered 4/2006

The incidence of adult respiratory distress syndrome (ARDS) in severe traumatic brain injury (TBI) is poorly reported. Recently, a new definition for ARDS was proposed, the Berlin definition. The percentage of patients represented by TBI in the Berlin criteria study is limited. This study describes the incidence and associated mortality of ARDS in TBI patients.The study was an analysis of the safety of erythropoietin administration and transfusion threshold on the incidence of ARDS in severe TBI patients. Three reviewers independently assessed all patients enrolled in the study for acute lung injury/ARDS using the Berlin and the American-European Consensus Conference (AECC) definitions. A Cox proportional hazards model was used to assess the relationship between ARDS and mortality and 6-month Glasgow Outcome Scale (GOS) score.Two hundred patients were enrolled in the study. Of the patients, 21% (41 of 200) and 26% (52 of 200) developed ARDS using the AECC and Berlin definitions, respectively, with a median time of 3 days (interquartile range, 3) after injury. ARDS by either definition was associated with increased mortality (p = 0.04) but not with differences in functional outcome as measured by the GOS score at 6 months. Adjusted analysis using the Berlin criteria showed an increased mortality associated with ADS (p = 0.01).Severe TBI is associated with an incidence of ARDS ranging from 20% to 25%. The incidence is comparable between the Berlin and AECC definitions. ARDS is associated with increased mortality in severe TBI patients, but further studies are needed to validate these findings.Epidemiologic study, level II.

Cerebral dysfunction caused by traumatic brain injury may adversely affect cerebral hemodynamics and oxygenation leading to worse outcomes if oxygen capacity is decreased due to anemia. In a randomized clinical trial of 200 patients comparing transfusion thresholds

Background The Final Rule regulations were developed to allow exception from informed consent (EFIC) to enable clinical trial research in emergency settings where major barriers exist for informed consent. There is little known evidence of the effect of the Final Rule in minority enrollment in clinical trials, particularly in traumatic brain injury (TBI) trials. A clinical trial funded by the National Institute of Neurological Disorders and Stroke was conducted to study the effects of erythropoietin on cerebral vascular dysfunction and anemia in subjects with TBI. There were periods of time when EFIC was and was not available for enrollment into the study. Purpose To explore the effect of EFIC availability on TBI trial enrollment of minority versus non-minority subjects. Methods Minority status of screened (n = 289) and enrolled (n = 191) TBI subjects was determined for this study. We tested for the presence of a minority and EFIC availability interaction in a multiple logistic regression model after controlling for EFIC and minority group main effects and other covariates. Results An interaction between the availability of EFIC minority and non-minority enrollment was not detected (odds ratio = 1.22; 95% confidence interval (CI) = 0.29–5.16). Limitations Our study was conducted at a single site, and the CI for the EFIC and minority interaction term was wide. Therefore, a small interaction effect cannot be ruled out. Conclusion EFIC increased the odds of being enrolled regardless of minority status.

Although national and state estimates of child obesity are available, data at these levels are insufficient to monitor effects of local obesity prevention initiatives. The purpose of this study was to examine regional changes in the prevalence of obesity due to statewide policies and programs among children in grades 4, 8, and 11 in Texas Health Services Regions (HSRs) between 2000-2002 and 2004-2005, and nine selected counties in 2004-2005. A cross-sectional, probability-based sample of 23,190 Texas students in grades 4, 8, and 11 were weighed and measured to obtain BMI. Obesity was >95th percentile for BMI by age/sex using Centers for Disease Control and Prevention growth charts. Child obesity prevalence significantly decreased between 2000-2002 and 2004-2005 for 4th grade students in the El Paso HSR (-7.0%, P = 0.005). A leveling off in the prevalence of obesity was noted for all other regions for grades 4, 8, and 11. County-level data supported the statistically significant decreases noted in the El Paso region. The reduction of child obesity levels observed in the El Paso area is one of the few examples of effective programs and policies based on a population-wide survey: in this region, a local foundation funded extensive regional implementation of community programs for obesity prevention, including an evidence-based elementary school-based health promotion program, adult nutrition and physical activity programs, and a radio and television advertising campaign. Results emphasize the need for sustained school, community, and policy efforts, and that these efforts can result in decreases in child obesity at the population level.

Importance There is limited information about the effect of erythropoietin or a high hemoglobin transfusion threshold after a traumatic brain injury. Objective To compare the effects of erythropoietin and 2 hemoglobin transfusion thresholds (7 and 10 g/dL) on neurological recovery after traumatic brain injury. Design, Setting, and Participants Randomized clinical trial of 200 patients (erythropoietin, n = 102; placebo, n = 98) with closed head injury who were unable to follow commands and were enrolled within 6 hours of injury at neurosurgical intensive care units in 2 US level I trauma centers between May 2006 and August 2012. The study used a factorial design to test whether erythropoietin would fail to improve favorable outcomes by 20% and whether a hemoglobin transfusion threshold of greater than 10 g/dL would increase favorable outcomes without increasing complications. Erythropoietin or placebo was initially dosed daily for 3 days and then weekly for 2 more weeks (n = 74) and then the 24- and 48-hour doses were stopped for the remainder of the patients (n = 126). There were 99 patients assigned to a hemoglobin transfusion threshold of 7 g/dL and 101 patients assigned to 10 g/dL. Interventions Intravenous erythropoietin (500 IU/kg per dose) or saline. Transfusion threshold maintained with packed red blood cells. Main Outcomes and Measures Glasgow Outcome Scale score dichotomized as favorable (good recovery and moderate disability) or unfavorable (severe disability, vegetative, or dead) at 6 months postinjury. Results There was no interaction between erythropoietin and hemoglobin transfusion threshold. Compared with placebo (favorable outcome rate: 34/89 [38.2%; 95% CI, 28.1% to 49.1%]), both erythropoietin groups were futile (first dosing regimen: 17/35 [48.6%; 95% CI, 31.4% to 66.0%], P = .13; second dosing regimen: 17/57 [29.8%; 95% CI, 18.4% to 43.4%], P P = .28). There was a higher incidence of thromboembolic events for the transfusion threshold of 10 g/dL (22/101 [21.8%] vs 8/99 [8.1%] for the threshold of 7 g/dL, odds ratio, 0.32 [95% CI, 0.12 to 0.79], P = .009). Conclusions and Relevance In patients with closed head injury, neither the administration of erythropoietin nor maintaining hemoglobin concentration of greater than 10 g/dL resulted in improved neurological outcome at 6 months. The transfusion threshold of 10 g/dL was associated with a higher incidence of adverse events. These findings do not support either approach in this setting. Trial Registration clinicaltrials.gov Identifier:NCT00313716