Ameliorating Racial Disparities in Vascular Risk Factor Management With Aggressive Medical Management in the SAMMPRIS Trial.

BACKGROUND: The WASID trial (Warfarin-Aspirin Symptomatic Intracranial Disease) and the SAMMPRIS trial (Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis) evaluated optimal management of symptomatic intracranial atherosclerotic stenosis. The aim of this retrospective, observational study was to determine whether aggressive medical management used in the SAMMPRIS trial ameliorated disparities in risk factor control between Black and non-Black patients. METHODS: The SAMMPRIS trial was a randomized controlled trial that enrolled patients with symptomatic intracranial atherosclerotic stenosis between November 2008 and April 2011. The frequency of risk factors at study entry (baseline) and mean levels of systolic blood pressure, diastolic blood pressure, LDL (low-density lipoprotein), hemoglobin A1c, and exercise level (quantified by physician-based assessment and counseling for exercise score) at baseline and at 1 year of follow-up were compared between Black (n=104) versus non-Black patients (n=347). RESULTS: Significant differences at baseline in Black patients (listed first) versus non-Black patients were age (57.5 versus 61.0 years; P=0.004), hypertension (95.2% versus 87.5%; P=0.027), diabetes (52.9% versus 39.7%; P=0.017), mean diastolic blood pressure (82.4 versus 79.5 mm Hg; P=0.035), and mean physician-based assessment and counseling for exercise score (2.7 versus 3.3; P=0.002). The mean diastolic blood pressure and mean physician-based assessment and counseling for exercise scores at 1 year in Black versus non-Black patients were 74.7 versus 75.5 mm Hg (P=0.575) and 4.2 versus 4.1 (P=0.593), respectively. No disparities in other modifiable risk factors emerged at 1 year. CONCLUSIONS: Significant differences in important risk factors (physical activity and diastolic blood pressure) at baseline between Black and non-Black patients resolved at 1 year, suggesting that aggressive medical management may have an important role in ameliorating disparities in risk factor control between Black and non-Black patients.

Neighborhood socioeconomic disadvantage measures in rehabilitation clinical trials: Lessons learned in recruitment.

PURPOSE: The Area Deprivation Index (ADI) measures the relative disadvantage of an individual or social network using US Census indicators. Although a strong re-hospitalization predictor, ADI has not been routinely incorporated into rehabilitation research. The purposes of this paper are to examine the use of ADI related to study recruitment, association with carepartner psychosocial factors, and recruitment strategies to increase participant diversity. METHODS: Descriptive analysis of baseline data from a pilot stroke carepartner-integrated therapy trial. Participants were 32 carepartners (N = 32; 62.5 % female; mean age 57.8 ± 13.0 years) and stroke survivors (mean age (60.6 ± 14.2) residing in an urban setting. Measures included ADI, Bakas Caregiver Outcome Scale, Caregiver Strain Index, and Family Assessment Device. RESULTS: Most carepartners were Non-Hispanic White participants (61.3 %), part or fully employed (43 %), with >$50,000 (67.7 %) income, and all had some college education. Most stroke survivors were Non-Hispanic White participants (56.3 %) with some college (81.3 %). Median ADI state deciles were 3.0 (interquartile range 1.5-5, range 1-9), and mean national percentiles were 41.7 ± 23.5 with only 6.3 % of participants from the most disadvantaged neighborhoods. For the more disadvantaged half of the state deciles, the majority were Black or Asian participants. No ADI and carepartner factors were statistically related. CONCLUSIONS: The use of ADI data highlighted a recruitment gap in this stroke study, lacking the inclusivity of participants from disadvantaged neighborhoods and with lower education. Using social determinants of health indicators to identify underrepresented neighborhoods may inform recruitment methods to target marginalized populations and broaden the generalizability of clinical trials.

Lipid Levels and Short-Term Risk of Recurrent Brain Infarcts in Symptomatic Intracranial Stenosis.

OBJECTIVES: Hyperlipidemia is a strong risk factor for intracranial atherosclerotic disease (ICAD) and clinical stroke recurrence. We explored the effect of serum lipid levels on subclinical infarct recurrence in the Mechanisms of earlY Recurrence in Intracranial Atherosclerotic Disease (MYRIAD) study. MATERIALS AND METHODS: We included enrolled MYRIAD patients with lipid measurements and brain MRI at baseline and brain MRI at 6-8 weeks. Infarct recurrence was defined as new infarcts in the territory of the symptomatic artery on brain MRI at 6-8 weeks compared to baseline brain MRI. We assessed the association between baseline total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) levels and recurrent infarct at 6-8 weeks using multivariable logistic regression. RESULTS: Among 74 patients (mean age 64.2±12.9 years, 59.5% were white, 60.8% men), 20 (27.0%) had new or recurrent infarcts. Mean HDL-C (37.2 vs. 43.9 mg/dL, P=0.037) was lower and TG (113.5 vs. 91.3 mg/dL, P=0.008) was higher while TC (199.8 vs. 174.3 mg/dL, P=0.061) and LDL-C (124.3 vs. 101.2 mg/dL, P=0.053) were nominally higher among those with recurrent infarcts than those without. LDL-C (adj. OR 1.022, 95% CI 1.004-1.040, P=0.015) and TG (adj. OR 1.009, 95% CI 1.001-1.016, P=0.021) were predictors of recurrent infarct at 6-8 weeks adjusting for other clinical and imaging factors. CONCLUSIONS: Baseline cholesterol markers can predict early infarct recurrence in patients with symptomatic ICAD. More intensive and rapid lipid lowering drugs may be required to reduce risk of early recurrence.

Predictors of Early Infarct Recurrence in Patients With Symptomatic Intracranial Atherosclerotic Disease.

BACKGROUND AND PURPOSE: While prior studies identified risk factors for recurrent stroke in patients with symptomatic intracranial atherosclerotic disease, few have assessed risk factors for early infarct recurrence. METHODS: We performed a post hoc analysis of the MYRIAD study (Mechanisms of Early Recurrence in Intracranial Atherosclerotic Disease) of intracranial atherosclerotic disease patients with recent (<21 days) stroke/transient ischemic attack, 50% to 99% stenosis and who underwent 6- to 8-week magnetic resonance imaging (MRI) per protocol. Infarct recurrence was defined as new infarcts in the territory of the symptomatic artery on brain MRI at 6 to 8 weeks compared to index brain MRI. Qualifying events and clinical and imaging outcomes were centrally ascertained by 2 independent reviewers. We assessed the association between baseline clinical and imaging variables and recurrent infarct in bivariate models and multivariable logistic regression to identify independent predictors of infarct recurrence. RESULTS: Of 105 enrolled patients in MYRIAD, 89 (84.8%) were included in this analysis (mean age, 64±12 years, 54 [60.7%] were male, and 53 [59.6%] were White). The median time from qualifying event to MRI was 51+16 days, on which 22 (24.7%) patients had new or recurrent infarcts. Younger age (57.7 versus 66.0 years; P<0.01), diabetes (32.6% versus 14.6%, P=0.05), index stroke (31.3% versus 4.6%, P=0.01), anterior circulation location of stenosis (29.7% versus 12.0%, P=0.08), number of diffusion-weighted imaging lesions (>1: 40.0%, 1: 26.9% versus 0: 4.4%, P<0.01), and borderzone infarct pattern (63.6% versus 25.0%, P=0.01) on baseline MRI were associated with new or recurrent infarcts. Age (adjusted odds ratio, 0.93 [95% CI, 0.89-0.98], P<0.01) and number of diffusion-weighted imaging lesions (adjusted odds ratio, 3.24 [95% CI, 1.36-7.71], P<0.01) were independently associated with recurrent infarct adjusting for hypertension, diabetes, and stenosis location (anterior versus posterior circulation). CONCLUSIONS: An index multi-infarct pattern is associated with early recurrent infarcts, a finding that might be explained by plaque instability and artery-to-artery embolism. Further investigation of plaque vulnerability in intracranial atherosclerotic disease is needed. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02121028.

The Myopic Shift in Aphakic Eyes in the Infant Aphakia Treatment Study After 10 Years of Follow-up.

OBJECTIVES: To report the myopic shift in the aphakic eyes of a cohort of children who underwent unilateral cataract surgery during infancy and were then followed longitudinally for 10.5 years. METHODS: One-half of the children enrolled in the Infant Aphakia Treatment Study (IATS) were randomized to aphakia and contact lens correction after unilateral cataract surgery. They then underwent ocular examinations using standardized protocols at prescribed time intervals until age 10.5 years. RESULTS: Thirty of 57 children randomized to aphakia remained aphakic at age 10.5, having undergone unilateral cataract surgery at a median age of 1.6 (IQR: 1.1-3.1) months. The median refractive error (RE) in the 57 eyes randomized to aphakia immediately after cataract surgery was 19.01 D (IQR: 16.98-20.49) compared to 10.38 D (IQR: 7.50-14.00) for the 30 eyes that remained aphakic at age 10.5 years. The mean change in RE in aphakic eyes was -2.11 D/year up to age 1.5 years, -0.68 D/year from 1.5 to 5.0 years, and -0.35 D/year from age 5 to 10.5 years. At age 10.5 years, 18 patients continued to wear a contact lens correction (silicone elastomer, n=6; gas permeable, n=6; hydrogel, n=5; and silicone hydrogel, n=1) (median RE, 12.50 D), 9 wore only spectacles (median RE, 4.00 D), and 4 wore no correction (median RE, 11.25 D) to correct their aphakic eye. CONCLUSIONS: The RE in aphakic eyes decreased by 44% from infancy to age 10.5 years. About two-thirds of children who remained aphakic at age 10.5 years continued to wear a contact lens.

Risk Factors Control and Early Recurrent Cerebral Infarction in Patients with Symptomatic Intracranial Atherosclerotic Disease.

BACKGROUND: The risk of early recurrent cerebral infarction (RCI) is high in patients with symptomatic intracranial atherosclerotic disease (IAD). We sought to determine the relationship between risk factor control and early RCI risk among patients with symptomatic IAD. METHODS: We analyzed participants with symptomatic IAD in the multi-center prospective observational MYRIAD study. Risk factor control was assessed at 6-8-week follow-up. Optimal risk factor control was defined by target systolic blood pressure, being non-smoker, target physical activity, and antiplatelet and antilipidemic therapy compliance. Age-adjusted associations were calculated between risk factor control and RCI determined by MRI-evident new infarcts in the territory of the stenotic vessel at 6-8 weeks from the index event. RESULTS: Among 82 participants with clinical and brain MRI information available 6-8 weeks after the index event (mean age 63.5 ±12.5 years, 62.2% men), RCI occurred in 21 (25.6%) cases. At 6-8-week follow-up, 37.8% had target systolic blood pressure, 92.7% were non-smokers, 51.2% had target physical activity, and 98.8% and 86.6% were compliant with antiplatelet and antilipidemic therapy, respectively. Optimal risk factor control increased from 4.9% at baseline to 19.5% at 6-8-week follow-up (p=0.01). None of the participants with optimal risk factor control at follow-up had RCI (0% vs. 31.8%, p<0.01). CONCLUSIONS: Only one-fifth of MYRIAD participants had optimal risk factor control during early follow-up. Approximately half and two-thirds had physical inactivity and uncontrolled systolic blood pressure, respectively. These risk factors may represent important therapeutic targets to prevent early RCI in patients with symptomatic IAD.

Infarct Recurrence in Intracranial Atherosclerosis: Results from the MyRIAD Study.

BACKGROUND: Intracranial atherosclerotic disease (ICAD) is a common cause of ischemic stroke with a high risk of clinical stroke recurrence. Multiple mechanisms may underlie cerebral ischemia in this condition. The study's objective is to discern the mechanisms of recurrent ischemia in ICAD through imaging biomarkers of impaired antegrade flow, poor distal perfusion, abnormal vasoreactivity, and artery-to-artery embolism. METHODS: This prospective multicenter observational study enrolled patients with recent (≤21 days) ischemic stroke or transient ischemic attack (TIA) caused by ICAD with 50-99% stenosis treated medically. We obtained baseline quantitative MRA (QMRA), perfusion MRI (PWI), transcranial Doppler vasoreactivity (VMR), and emboli detection studies (EDS). The primary outcome was ischemic stroke in the territory of the stenotic artery within 1 year of follow-up; secondary outcomes were TIA at 1 year and new infarcts in the territory on MRI at 6-8 weeks. RESULTS: Amongst 102 of 105 participants with clinical follow-up (mean 253±131 days), the primary outcome occurred in 8.8% (12.7/100 patient-years), while 5.9% (8.5/100 patient-years) had a TIA. A new infarct in the territory of the symptomatic artery was noted in 24.7% at 6-8 weeks. A low flow state on QMRA was noted in 25.5%, poor distal perfusion on PWI in 43.5%, impaired vasoreactivity on VMR in 67.5%, and microemboli on EDS in 39.0%. No significant association was identified between these imaging biomarkers and primary or secondary outcomes. CONCLUSIONS: Despite intensive medical management in ICAD, there is a high risk of clinical cerebrovascular events at 1 year and an even higher risk of new imaging-evident infarcts in the subacute period after index stroke. Hemodynamic and plaque instability biomarkers did not identify a higher risk group. Further work is needed to identify mechanisms of ischemic stroke and infarct recurrence and their consequence on long-term physical and cognitive outcomes. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02121028.

Dual Antiplatelet Therapy Beyond 90 days in Symptomatic Intracranial Stenosis in the SAMMPRIS Trial.

BACKGROUND: The safety and efficacy of dual antiplatelet use for symptomatic intracranial atherosclerosis beyond 90 days is unknown. Data from SAMMPRIS was used to determine if dual antiplatelet therapy (DAPT) beyond 90 days impacted the risk of ischemic stroke and hemorrhage. METHODS: This post hoc exploratory analysis from SAMMPRIS included patients who did not have a primary endpoint within 90 days after enrollment (n = 397). Patients in both the aggressive medical management (AMM) and percutaneous transluminal angioplasty and stenting (PTAS) arms were included. Baseline features and outcomes during follow-up were compared between patients who remained on DAPT beyond 90 days (on clopidogrel) and patients who discontinued clopidogrel and remained on aspirin alone at 90 days (off clopidogrel) using Fisher's exact tests. RESULTS: The stroke rate was numerically lower in the group on clopidogrel vs off clopidogrel among both the AMM alone arm (6.0% versus 10.8%, p = 0.31) and the PTAS arm (8.7% versus 9.8%; p = 0.82), but the difference was not significant. The major hemorrhage rates were numerically higher in the group on clopidogrel vs. off clopidogrel group among both the AMM alone arm (4.0% versus 2.5%; p = 0.67) and the PTAS arm (10.9% versus 3.5%; p = 0.08), but were not significant. CONCLUSION: This exploratory analysis suggests that prolonged DAPT use may lower the risk of stroke in medically treated patients with intracranial stenosis but may increase the risk of major hemorrhage.

Poststroke Montreal Cognitive Assessment and Recurrent Stroke in Patients With Symptomatic Intracranial Atherosclerosis.

BACKGROUND AND PURPOSE: Cognitive impairment occurs in 20%-40% of stroke patients and is a predictor of long-term morbidity and mortality. In this study, we aim to determine the association between poststroke cognitive impairment and stroke recurrence risk, in patients with anterior versus posterior circulation intracranial stenosis. METHODS: This is a post-hoc analysis of the Stenting and Aggressive Medical Therapy for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) trial. The primary predictor was poststroke cognitive function measured by Montreal Cognitive Assessment (MOCA) at 3-6 months and the primary outcome was recurrent ischemic stroke. We used univariate and multivariable cox-regression models to determine the associations between MOCA at 3-6 months and recurrent stroke. RESULTS: Of the 451 patients enrolled in SAMMPRIS, 393 patients met the inclusion criteria. The mean age of the sample (in years) was 59.5 ± 11.3, 62.6% (246 of 393) were men. Fifty patients (12.7%) had recurrent ischemic stroke during a mean follow up of 2.7 years. The 3-6 month MOCA score was performed on 351 patients. In prespecified multivariable models, there was an association between 3 and 6 month MOCA and recurrent stroke (hazard ratio [HR] per point increase .93 95% confidence interval [CI] .88-.99, P = .040). This effect was present in anterior circulation stenosis (adjusted HR per point increase .92 95% CI .85-0.99, P = .022) but not in posterior circulation artery stenosis (adjusted HR per point increase 1.00 95% .86-1.16, P = .983). CONCLUSIONS: Overall, we found weak associations and trends between MoCA at 3-6 months and stroke recurrence but more notable and stronger associations in certain subgroups. Since our study is underpowered, larger studies are needed to validate our findings and determine the mechanism(s) behind this association.

Hemodynamic Markers in the Anterior Circulation as Predictors of Recurrent Stroke in Patients With Intracranial Stenosis.

Background and Purpose- Although aggressive medical therapy was superior to stenting in the SAMMPRIS trial (Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis), the stroke rate in the medical arm was still high. The aim of this study was to determine the association between hemodynamic markers (borderzone infarct pattern and impaired collateral flow on baseline imaging) and rates of recurrent stroke in patients treated medically in SAMMPRIS. Methods- This was a post hoc analysis of patients whose qualifying event for SAMMPRIS was an infarct in the territory of a stenotic middle cerebral artery or intracranial carotid artery. Infarcts were adjudicated as involving primarily internal or cortical borderzone territories, the core middle cerebral artery territory, or perforator territories, and collateral flow was assessed according to a standard scale (American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology). Log-rank tests and χ2 tests were performed to assess associations of infarct patterns and collateral flow with rates of recurrent stroke. Results- Of 101 patients who qualified, 14 of 53 (26.4%) with borderzone infarcts, 2 of 24 (8.3%) with core middle cerebral artery infarcts, and 3 of 24 (12.5%) with perforator infarcts had a recurrent stroke in the territory (P=0.14 for comparing the 3 groups, P=0.052 for borderzone versus nonborderzone). Of 82 patients with collateral flow assessment, 30 of 43 (70%) with borderzone infarcts, 7 of 19 (37%) with core middle cerebral artery infarcts, and 11 of 20 (55%) with perforator infarcts had impaired collateral flow distal to the stenosis (P=0.049). Patients with borderzone infarcts and impaired collateral flow had the highest risk of recurrent stroke (37%). Conclusions- Borderzone infarcts and impaired collateral flow identify a subgroup of patients with intracranial stenosis who are at particularly high risk of recurrent stroke on medical treatment. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT00576693.

Impact of Baseline Features and Risk Factor Control on Cognitive Function in the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis Trial.

BACKGROUND: Cerebrovascular disease is an important cause of cognitive impairment. The aim of this study is to report the relationship between cognitive function and risk factors at baseline and during follow-up in the Stenting and Aggressive Medical Management for Preventing Recurrent stroke in Intracranial Stenosis (SAMMPRIS) trial. METHODS: Subjects in the SAMMPRIS trial were included in this study. In order to have an assessment of cognitive function independent of stroke, patients with a stroke as a qualifying event whose deficits included aphasia or neglect were excluded from these analyses as were those with a cerebrovascular event during follow-up. The Montreal Cognitive Assessment (MoCA) score was used to assess cognitive impairment at baseline, 4 months, 12 months and closeout. Cognitive impairment was defined as MoCA < 26. A multivariate analysis was performed to determine what risk factors were independent predictors of cognitive function at baseline, 12 months and closeout. Among patients randomized to aggressive medical management only, the percentage of patients with cognitive impairment was compared between patients in versus out of target for each risk factor at 12 months and closeout. RESULTS: Of the 451 patients in SAMMPRIS, 371 patients met the inclusion criteria. MoCA < 26 was present in 55% at baseline. Older age and physical inactivity were associated with cognitive impairment at baseline. Older age, non-white race, lower baseline body mass index, and baseline cognitive impairment were associated with cognitive impairment at 12 months. In the aggressive medical management group, at 12 months, physical inactivity during follow-up was the strongest risk factor associated with cognitive impairment. CONCLUSION: Cognitive impairment is common in patients with severe symptomatic intracranial atherosclerosis. Physical inactivity at baseline and during follow-up is a strong predictor of cognitive impairment.

Nonprocedural Symptomatic Infarction and In-Stent Restenosis After Intracranial Angioplasty and Stenting in the SAMMPRIS Trial (Stenting and Aggressive Medical Management for the Prevention of Recurrent Stroke in Intracranial Stenosis).

BACKGROUND AND PURPOSE: The purpose of this study was to investigate the frequency of symptomatic in-stent restenosis (ISR) and its contribution to nonprocedural symptomatic infarction in the SAMMPRIS trial (Stenting and Aggressive Medical Management for the Prevention of Recurrent Stroke in Intracranial Stenosis). METHODS: Patients without a periprocedural primary end point were followed up to determine the occurrence of any of the following events: ischemic stroke, cerebral infarct with temporary signs, or transient ischemic attack in the territory of the stented artery. Vascular imaging performed after these events was reviewed for ISR. Annual rates for symptomatic ISR were calculated using Kaplan-Meier estimates. RESULTS: Of 183 patients in the stenting group without a periprocedural primary end point, 27 (14.8%) had a symptomatic infarction (stroke or cerebral infarct with temporary signs) and 16 (8.7%) had transient ischemic attack alone in the territory during a median follow-up of 35.0 months. Of the 27 patients with infarctions, 17 (9.3%) had an ischemic stroke and 10 (5.5%) had a cerebral infarct with temporary signs alone. Adequate vascular imaging to evaluate ISR was available in 24 patients with infarctions (showing ISR in 16 [66.7%]) and in 10 patients with transient ischemic attack alone (showing ISR in 8 [80%]). The 1-, 2-, and 3-year rates (with 95% confidence limits) for symptomatic ISR in the SAMMPRIS stent cohort were 9.6% (6.1%-14.9%), 11.3% (7.5%-17.0%), and 14.0% (9.6%-20.2%), respectively. CONCLUSIONS: Symptomatic ISR occurred in at least 1 of 7 patients in SAMMPRIS by 3 years of follow-up and was likely responsible for the majority of nonprocedural cerebral infarctions. CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov. Unique identifier: NCT00576693.

Globe Axial Length Growth at Age 5 Years in the Infant Aphakia Treatment Study.

PURPOSE: To report the longitudinal change in axial length (AL) from the time of unilateral cataract surgery at age 1 to 7 months to age 5 years, and to compare AL growth of operated eyes with that of fellow unoperated eyes. DESIGN: Comparative case series. PARTICIPANTS: Infants enrolled in the Infant Aphakia Treatment Study (IATS). METHODS: The AL at baseline and age 5 years and change in AL were analyzed relative to treated versus fellow eye, visual outcome, and treatment modality (contact lens [CL] vs. intraocular lens [IOL]). Eyes with glaucoma or glaucoma suspect were excluded from primary analysis but reported separately. MAIN OUTCOME MEASURES: The AL growth from preoperative to age 5 years. RESULTS: Seventy patients were eligible; however, AL data for both eyes were available for 64 patients at baseline and 69 patients at age 5 years. The AL was significantly different between treated and fellow eyes preoperatively (18.1 vs. 18.7 mm, P < 0.0001) and at the final follow-up (21.4 vs. 22.1 mm, P = 0.0004). The difference in AL growth between treated and fellow eyes was not significant (3.3 vs. 3.5 mm, P = 0.31). The change in AL in eyes was similar with both treatments (CL 3.2 mm and IOL 3.4 mm, P = 0.53) and did not correlate with visual outcomes (P = 0.85). Eyes receiving additional surgery to clear the visual axis opacification grew significantly more compared with eyes not receiving surgery to clear the visual axis (3.8 vs. 2.7 mm, P = 0.013). Patients with glaucoma showed significantly more eye growth (5.7 mm) than those without glaucoma (3.3 mm) and glaucoma suspects (4.3 mm). CONCLUSIONS: Eyes treated for monocular cataract in infancy have axial growth similar to that of fellow eyes, despite having a shorter AL at the time of surgery. The change in AL in eyes was similar with both treatments (CL and IOL), did not correlate with visual outcomes, and was higher in eyes receiving additional surgery to clear the visual axis or eyes diagnosed with glaucoma.

Myopic Shift 5 Years after Intraocular Lens Implantation in the Infant Aphakia Treatment Study.

PURPOSE: To report the myopic shift at 5 years of age after cataract surgery with intraocular lens (IOL) implantation for infants enrolled in the Infant Aphakia Treatment Study (IATS). METHODS: Refractions were performed at 1 month and every 3 months postoperatively until age 4 years and then at ages 4.25, 4.5, and 5 years. The change in refraction over time was estimated by linear mixed model analysis. RESULTS: Intraocular lens implantation was completed in 56 eyes; 43 were analyzed (median age, 2.4 months; range, 1.0-6.8 months). Exclusions included 11 patients with glaucoma, 1 patient with Stickler syndrome, and 1 patient with an IOL exchange at 8 months postoperatively. The mean rate of change in a myopic direction from 1 month after cataract surgery to age 1.5 years was 0.35 diopters (D)/month (95% confidence interval [CI], 0.29-0.40 D/month); after age 1.5 years, the mean rate of change in a myopic direction was 0.97 D/year (95% CI, 0.66-1.28 D/year). The mean refractive change was 8.97 D (95% CI, 7.25-10.68 D) at age 5 years for children 1 month of age at surgery and 7.22 D (95% CI, 5.54-8.91 D) for children 6 months of age at surgery. The mean refractive error at age 5 years was -2.53 D (95% CI, -4.05 to -1.02). CONCLUSIONS: After IOL implantation during infancy, the rate of myopic shift occurs most rapidly during the first 1.5 years of life. Myopic shift varies substantially among patients. If the goal is emmetropia at age 5 years, then the immediate postoperative hypermetropic targets should be +10.5 D at 4 to 6 weeks and +8.50 D from 7 weeks to 6 months. However, even using these targets, it is likely that many children will require additional refractive correction given the high variability of refractive outcomes.

Is There Benefit from Stenting on Cognitive Function in Intracranial Atherosclerosis?

BACKGROUND: Revascularization of stenotic cerebral arteries is hypothesized to improve cognition by increasing cerebral perfusion. AIMS: We compared cognition impairment among patients treated with percutaneous angioplasty and stenting (PTAS) and aggressive medical management (AMM) versus AMM alone in the Stenting versus Aggressive Medical Therapy for Intracranial Arterial Stenosis (SAMMPRIS) Trial. METHODS: In SAMMPRIS, 451 patients with recent transient ischemic attack or stroke attributed to 70-99% intracranial stenosis were randomized to PTAS plus AMM or AMM alone. Patients who had stroke as the qualifying event with National Institutes of Health Stroke Scale indicating aphasia or neglect were excluded from these analyses. Patients with a cerebrovascular event (ischemic stroke, cerebral infarct with temporary signs or intracranial hemorrhage) during follow-up were excluded from follow-up visit analyses. The Montreal Cognitive Assessment (MoCA) score was used to assess cognition impairment at baseline, 4 months, 12 months and closeout. Cognitive impairment was defined as MoCA <26. Mean MoCA scores and the percentage of patients with cognitive impairment were compared between treatment groups at each time point using t tests and chi-square tests. Differences in MoCA mean at baseline and follow-up time points were compared using mixed model repeated measures ANOVA and Tukey-Kramer tests. RESULTS: There were no significant differences between the treatment groups for mean MoCA at any time point. Mean MoCA scores improved in both groups. The percentage of patients with cognitive impairment in the AMM versus PTAS groups was not significantly different at any time point. CONCLUSIONS: Revascularization with PTAS showed no improvement in cognitive impairment over AMM alone among patients who did not have recurrent cerebrovascular events during follow-up.

Effect of positive perioperative donor and recipient respiratory bacterial cultures on early post-transplant outcomes in lung transplant recipients.

BACKGROUND: It is standard practice to administer prophylactic antibiotics post lung transplantation. However, no studies have evaluated the impact of culture positivity. The purpose of this study was to evaluate early post-transplant outcomes of culture-positive and culture-negative lung transplant (LT) recipients and the appropriateness of the empiric regimens used. METHODS: Adult patients who received an LT at Emory University Hospital between January 1, 2010 and August 31, 2015 were reviewed and stratified into three groups: (i) culture-positive appropriate empiric treatment, (ii) culture-positive inappropriate empiric treatment, and (iii) culture-negative. Antibiotics were defined as appropriate if bacteria were sensitive to the empiric regimen. The primary endpoint was 30-day mortality. Secondary endpoints included hospital length of stay (LOS), intensive care unit (ICU) LOS, percent neutrophil count in a bronchoalveolar lavage (BAL) sample, presence of airway ischemia, and appropriateness of the empiric antibiotic regimen. RESULTS: Nine, zero, and four patients died within 30 days in the culture-positive appropriate (n = 113), culture-positive inappropriate (n = 5), and culture-negative groups (n = 29) (P = .564) respectively. The median hospital LOS was 19, 16, and 15 days respectively. Median ICU LOS was 6, 5, and 7 respectively. The respective percent neutrophil counts in the BAL fluid were 79, 83, and 65. The presence of airway ischemia was only documented in eight patients, all in the culture-positive appropriate group. CONCLUSION: We did not identify an association between antibiotic appropriateness and 30-day mortality, hospital LOS, or ICU LOS in post-LT recipients.

Contact networks in the emergency department: Effects of time, environment, patient characteristics, and staff role.

Emergency departments play a critical role in the public health system, particularly in times of pandemic. Infectious patients presenting to emergency departments bring a risk of cross-infection to other patients and staff through close proximity interactions or contacts. To understand factors associated with cross-infection risk, we measured close proximity interactions of emergency department staff and patients by radiofrequency identification in a working emergency department. The number of contacts (degree) is not related to patient demographic characteristics. However, the amount of time in close proximity (weighted degree) of patients with ED personnel did differ, with black patients having approximately 15 min more contact with staff than non-white patients. Patients arriving by EMS had fewer contacts with other patients than patients arriving by other means. There are differences in the number of contacts based on staff role and arrival mode. When crowding is low, providers have the most contact time with patients, while administrative staff have the least. However, when crowding is high, this differential is reversed. The effect of arrival mode is modified by the extent of crowding. When crowding is low, patients arriving by EMS had longer contact with administrative staff, compared to patients arriving by other means. However, when crowding is high, patients arriving by EMS had less contact with administrative staff compared to patients arriving by other means. Our findings should help designers of emergency care focus on higher risk situations for transmission of dangerous pathogens in an emergency department. For instance, the effects of arrival and crowding should be considered as targets for engineering or architectural interventions that could artificially increase social distances.

Efficacy and Safety of Glutamine-supplemented Parenteral Nutrition in Surgical ICU Patients: An American Multicenter Randomized Controlled Trial.

OBJECTIVE: To determine whether glutamine (GLN)-supplemented parenteral nutrition (PN) improves clinical outcomes in surgical intensive care unit (SICU) patients. SUMMARY BACKGROUND DATA: GLN requirements may increase with critical illness. GLN-supplemented PN may improve clinical outcomes in SICU patients. METHODS: A parallel-group, multicenter, double-blind, randomized, controlled clinical trial in 150 adults after gastrointestinal, vascular, or cardiac surgery requiring PN and SICU care. Patients were without significant renal or hepatic failure or shock at entry. All received isonitrogenous, isocaloric PN [1.5 g/kg/d amino acids (AAs) and energy at 1.3× estimated basal energy expenditure]. Controls (n = 75) received standard GLN-free PN (STD-PN); the GLN group (n = 75) received PN containing alanyl-GLN dipeptide (0.5 g/kg/d), proportionally replacing AA in PN (GLN-PN). Enteral nutrition (EN) was advanced and PN weaned as indicated. Hospital mortality and infections were primary endpoints. RESULTS: Baseline characteristics, days on study PN and daily macronutrient intakes via PN and EN, were similar between groups. There were 11 hospital deaths (14.7%) in the GLN-PN group and 13 deaths in the STD-PN group (17.3%; difference, -2.6%; 95% confidence interval, -14.6% to 9.3%; P = 0.66). The 6-month cumulative mortality was 31.4% in the GLN-PN group and 29.7% in the STD-PN group (P = 0.88). Incident bloodstream infection rate was 9.6 and 8.4 per 1000 hospital days in the GLN-PN and STD-PN groups, respectively (P = 0.73). Other clinical outcomes and adverse events were similar. CONCLUSIONS: PN supplemented with GLN dipeptide was safe, but did not alter clinical outcomes among SICU patients.

Does the Stenting Versus Aggressive Medical Therapy Trial Support Stenting for Subgroups With Intracranial Stenosis?

BACKGROUND AND PURPOSE: Although the Stenting Versus Aggressive Medical Therapy for Intracranial Arterial Stenosis (SAMMPRIS) trial showed that medical therapy alone was superior to stenting plus medical therapy for preventing recurrent strokes in patients with symptomatic intracranial stenosis, we determined whether SAMMPRIS supported the use of stenting in any subpopulations of patients with symptomatic intracranial arterial stenosis. METHODS: The primary outcome, 30-day stroke and death and later strokes in the territory of the qualifying artery, was compared in those with and without baseline factors in the 2 treatment arms, percutaneous transluminal angioplasty and stenting (PTAS) plus aggressive medical therapy versus aggressive medical therapy alone. Baseline factors included sex, age, race, diabetes mellitus, hypertension, lipid disorder, smoking status, type of qualifying event, qualifying event hypoperfusion symptoms, use of antithrombotic or proton pump inhibitor at baseline, days to enrollment, old infarcts in the same territory, percent stenosis, other artery stenosis, and location of the symptomatic artery. RESULTS: A total of 451 patients were enrolled, 227 randomized to aggressive medical therapy and 224 to PTAS. Of all variables evaluated, the observed 2-year event rates were higher with PTAS than with aggressive medical therapy in the vast majority and the interaction with treatment was not statistically significant for any of the factors. CONCLUSIONS: The SAMMPRIS results do not provide evidence to support the use of PTAS using the Wingspan stent system compared with medical treatment in any examined subpopulation of patients with symptomatic intracranial stenosis, including those with qualifying event hypoperfusion symptoms. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00576693.

Intracranial stenosis: impact of randomized trials on treatment preferences of US neurologists and neurointerventionists.

BACKGROUND AND PURPOSE: Medical and endovascular treatment options for stroke prevention in patients with symptomatic intracranial stenosis have evolved over the past several decades, but the impact of 2 major multicenter randomized stroke prevention trials on physician practices has not been studied. We sought to determine changes in US physician treatment choices for patients with intracranial atherosclerotic stenosis (ICAS) following 2 NIH-funded clinical trials that studied medical therapies (antithrombotic agents and risk factor control) and percutaneous transluminal angioplasty and stenting (PTAS). METHODS: Anonymous surveys on treatment practices in patients with ICAS were sent to physicians at 3 time points: before publication of the NIH-funded Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) trial (pre-WASID survey, 2004), 1 year after WASID publication (post-WASID survey, 2006) and 1 year after the publication of the NIH-funded Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) trial (post-SAMMPRIS survey, 2012). Neurologists were invited to participate in the pre-WASID survey (n=525). Neurologists and neurointerventionists were invited to participate in the post-WASID (n=598) and post-SAMMPRIS (n=2,080) surveys. The 3 surveys were conducted using web-based survey tools delivered by E-mail, and a fax-based response form delivered by E-mail and conventional mail. Data were analyzed using the χ2 test. RESULTS: Before WASID, there was equipoise between warfarin and aspirin for stroke prevention in patients with ICAS. The number of respondents who recommended antiplatelet treatment for ICAS increased across all 3 surveys for both anterior circulation (pre-WASID=44%, post-WASID=85%, post-SAMMPRIS=94%) and posterior circulation (pre-WASID=36%, post-WASID=74%, post-SAMMPRIS=83%). The antiplatelet agent most commonly recommended after WASID was aspirin, but after SAMMPRIS it was the combination of aspirin and clopidogrel. The percentage of neurologists who recommended PTAS in >25% of ICAS patients increased slightly from pre-WASID (8%) to post-WASID surveys (12%), but then decreased again after SAMMPRIS (6%). The percentage of neurointerventionists who recommended PTAS in >25% of ICAS patients decreased from post-WASID (49%) to post-SAMMPRIS surveys (17%). CONCLUSIONS: The surveyed US physicians' recommended treatments for ICAS differed over the 3 survey periods, reflecting the results of the 2 NIH-funded clinical trials of ICAS and suggesting that these clinical trials changed practice in the USA.