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OBJECTIVE The authors of this study evaluated the safety and efficacy of stereotactic laser ablation (SLA) for the treatment of drug-resistant epilepsy (DRE) in children. METHODS Seventeen North American centers were enrolled in the study. Data for pediatric patients with DRE who had been treated with SLA between 2008 and 2018 were retrospectively reviewed. RESULTS A total of 225 patients, mean age 12.8 ± 5.8 years, were identified. Target-of-interest (TOI) locations included extratemporal (44.4%), temporal neocortical (8.4%), mesiotemporal (23.1%), hypothalamic (14.2%), and callosal (9.8%). Visualase and NeuroBlate SLA systems were used in 199 and 26 cases, respectively. Procedure goals included ablation (149 cases), disconnection (63), or both (13). The mean follow-up was 27 ± 20.4 months. Improvement in targeted seizure type (TST) was seen in 179 (84.0%) patients. Engel classification was reported for 167 (74.2%) patients; excluding the palliative cases, 74 (49.7%), 35 (23.5%), 10 (6.7%), and 30 (20.1%) patients had Engel class I, II, III, and IV outcomes, respectively. For patients with a follow-up ≥ 12 months, 25 (51.0%), 18 (36.7%), 3 (6.1%), and 3 (6.1%) had Engel class I, II, III, and IV outcomes, respectively. Patients with a history of pre-SLA surgery related to the TOI, a pathology of malformation of cortical development, and 2+ trajectories per TOI were more likely to experience no improvement in seizure frequency and/or to have an unfavorable outcome. A greater number of smaller thermal lesions was associated with greater improvement in TST. Thirty (13.3%) patients experienced 51 short-term complications including malpositioned catheter (3 cases), intracranial hemorrhage (2), transient neurological deficit (19), permanent neurological deficit (3), symptomatic perilesional edema (6), hydrocephalus (1), CSF leakage (1), wound infection (2), unplanned ICU stay (5), and unplanned 30-day readmission (9). The relative incidence of complications was higher in the hypothalamic target location. Target volume, number of laser trajectories, number or size of thermal lesions, or use of perioperative steroids did not have a significant effect on short-term complications. CONCLUSIONS SLA appears to be an effective and well-tolerated treatment option for children with DRE. Large-volume prospective studies are needed to better understand the indications for treatment and demonstrate the long-term efficacy of SLA in this population.

Background Previous studies have shown varying results between lumbosacral transforaminal epidural steroid injections (TFESIs) performed with particulate versus non-particulate corticosteroids. The purpose of this study was to investigate the difference in pain relief and functional improvement between particulate and non-particulate lumbosacral TFESIs in patients who had undergone both injections, sequentially. Methods This was a self-controlled, retrospective study of 20 patients who underwent both a methylprednisolone and a dexamethasone TFESI to the same vertebral level and side. Primary outcomes included pain relief according to the visual analogue scale (VAS) and functional improvement determined by a yes/no answer to questions regarding mobility and the activities of daily living. Post-injection data was recorded at 2, 3, and 6 months. Results A decrease in VAS scores of -3.4 ± 3.0 (mean ± standard deviation), -3.1 ± 3.1, and -2.8 ± 3.4 was seen for the methylprednisolone group at 2, 3, and 6 months, respectively. Similar decreases of -3.9 ± 3.5, -3.4 ± 2.8, and -2.3 ± 3.4 were seen in the dexamethasone group. There was no significant difference in pain relief at any point between the two medications. The percentage of subjects who reported improved function at 2, 3, and 6 months was 65%, 51%, and 41%, respectively, for the methylprednisolone group and 75%, 53%, and 42% for the dexamethasone group. Conclusions These findings support the use of non-particulate corticosteroids for lumbosacral TFESIs in the context of documented safety concerns with particulate corticosteroids.

Purpose To assess the impact of two TYR hypomorphic alleles (R402Q and S192Y) on foveal pit and FAZ morphology. Design Prospective cross-sectional study Participants One hundred sixty-four participants with normal vision (67 males and 97 females; mean ± SD age = 30.5 ± 12.8 years) were recruited. Methods Sequencing of over 100 pigmentation-related genes was performed, and results were reviewed for the presence or absence of the TYR polymorphisms R402Q (rs1126809) and S192Y (rs1042602). Volumetric scans of the macula were obtained for each participant using optical coherence tomography (OCT) and retinal thickness maps were analyzed using custom software. OCT angiography (OCT-A) was used to image the foveal avascular zone (FAZ) which was manually segmented and measured. Linear mixed model analysis was used to assess associations between genotype and foveal pit morphology Main Outcome Measures Foveal pit depth, diameter, volume and FAZ area in relation to the presence of hypomorphic alleles R402Q and S192Y on the TYR gene. Results Heterozygosity for the TYR R402Q allele was associated with decreased pit diameter (p = 0.0094) and decreased FAZ area (p = 0.025). Homozygosity for the TYR R402Q allele was associated with reduced pit volume (p = 0.0005), decreased pit depth (p = 0.007), reduced pit diameter (p = 0.0052) and reduced FAZ area (p = 0.0012). Homozygosity for TYR S192Y was associated with reduced FAZ area (p = 0.016). Heterozygosity for the TYR S192Y allele was not associated with differences in foveal pit depth, diameter, volume or FAZ area (p > 0.05). Conclusion While the role of the TYR R402Q and S192Y hypomorphic alleles in albinism remains controversial, our data suggest that these variants contribute to the extensive inter-individual variability in foveal morphology in the normal population. Our results contribute to the evolving picture of the relationship between ocular pigmentation and foveal morphology.

Among four sub-patterns of Gleason grade 4 prostate cancer, voluminous evidence supports that the cribriform pattern holds an unfavorable prognostic impact, as compared with poorly-formed, fused, or glomeruloid. The International Society of Urological Pathology (ISUP) recommends specifying whether invasive grade 4 cancer is cribriform. Recently, ISUP experts published a consensus definition of cribriform pattern highlighting criteria that distinguish it from mimickers. The current study aimed to analyze morphologic features separately to identify those that define the essence of the cribriform pattern. Thirty-two selected photomicrographs were classified by 12 urologic pathologists as: definitely cribriform cancer, probably cribriform, unsure, probably not cribriform, or definitely not cribriform. Consensus was defined as 9/12 agree or disagree, with ≤1 strongly supporting the opposite choice. Final consensus was achieved in 21 of 32 cases. Generalized estimating equation (GEE) model with logit link was fitted to estimate effect of multiple morphologic predictors. Fisher exact test was used for categorical findings. Presence of intervening stroma precluded calling cribriform cancer (p = 0.006). Mucin presence detracted (p = 0.003) from willingness to call cribriform cancer (only 3 cases had mucin). Lumen number was associated with cribriform consensus (p = 0.0006), and all consensus cases had ≥9 lumens. Predominant papillary pattern or an irregular outer boundary detracted (p = NS). Invasive cribriform carcinoma should have absence of intervening stroma, and usually neither papillary pattern, irregular outer boundary, nor very few lumens. Setting the criteria for cribriform will help prevent over- or undercalling this important finding.

The goal of this study is to understand and mitigate the effects of wounds on acute radiation syndrome (ARS) and delayed effects of acute radiation exposure (DEARE), for preparedness against a radiological attack or accident. Combined injuries from concomitant trauma and radiation are likely in these scenarios. Either exacerbation or mitigation of radiation damage by wound trauma has been previously reported in preclinical studies. Female WAG/RijCmcr rats received 13 Gy X-rays, with partial-body shielding of one leg. Within 2 h, irradiated rats and non-irradiated controls were given full-thickness skin wounds with or without lisinopril, started orally 7 days after irradiation. Morbidity, skin wound area, breathing interval and blood urea nitrogen were measured up to 160 days post-irradiation to independently evaluate wound trauma and DEARE. Wounding exacerbated morbidity in irradiated rats between 5 and 14 days post-irradiation (during the ARS phase), and irradiation delayed wound healing. Wounding did not alter delayed morbidities from radiation pneumonitis or nephropathy after 30 days post-irradiation. Lisinopril did not mitigate wound healing, but markedly decreased morbidity during DEARE from 31 through 160 days. The results derived from this unique model of combined injuries suggest different molecular mechanisms of injury and healing of ARS and DEARE after radiation exposure.

Purpose To evaluate how metrics used to describe the cone mosaic change in response to simulated photoreceptor undersampling (i.e., cell loss or misidentification). Methods Using an adaptive optics ophthalmoscope, we acquired images of the cone mosaic from the center of fixation to 10° along the temporal, superior, inferior, and nasal meridians in 20 healthy subjects. Regions of interest (n = 1780) were extracted at regular intervals along each meridian. Cone mosaic geometry was assessed using a variety of metrics - density, density recovery profile distance (DRPD), nearest neighbor distance (NND), intercell distance (ICD), farthest neighbor distance (FND), percentage of six-sided Voronoi cells, nearest neighbor regularity (NNR), number of neighbors regularity (NoNR), and Voronoi cell area regularity (VCAR). The "performance" of each metric was evaluated by determining the level of simulated loss necessary to obtain 80% statistical power. Results Of the metrics assessed, NND and DRPD were the least sensitive to undersampling, classifying mosaics that lost 50% of their coordinates as indistinguishable from normal. The NoNR was the most sensitive, detecting a significant deviation from normal with only a 10% cell loss. Conclusions The robustness of cone spacing metrics makes them unsuitable for reliably detecting small deviations from normal or for tracking small changes in the mosaic over time. In contrast, regularity metrics are more sensitive to diffuse loss and, therefore, better suited for detecting such changes, provided the fraction of misidentified cells is minimal. Combining metrics with a variety of sensitivities may provide a more complete picture of the integrity of the photoreceptor mosaic.

The contents of this article were developed under a grant from the National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR grant number 90AR5022-01-00 Formerly H133P140023-14). NIDILRR is a Center within the Administration for Community Living (ACL), Department of

Purpose To examine repeatability and reproducibility of ellipsoid zone (EZ) width measurements in patients with retinitis pigmentosa (RP) using a longitudinal reflectivity profile (LRP) analysis. Methods We examined Bioptigen optical coherence tomography (OCT) scans from 48 subjects with RP or Usher syndrome. Nominal scan lengths were 6, 7, or 10 mm, and the lateral scale of each scan was calculated using axial length measurements. LRPs were generated from OCT line scans, and the peak corresponding to EZ was manually identified using ImageJ. The locations at which the EZ peak disappeared were used to calculate EZ width. Each scan was analyzed twice by each of two observers, who were masked to their previous measurements and those of the other observer. Results On average, horizontal width (HW) was significantly greater than vertical width (VW), and there was high interocular symmetry for both HW and VW. We observed excellent intraobserver repeatability with intraclass correlation coefficients (ICCs) ranging from 0.996 to 0.998 for HW and VW measurements. Interobserver reproducibility was also excellent for both HW (ICC = 0.989; 95% confidence interval [CI] = 0.983-0.995) and VW (ICC = 0.991; 95% CI = 0.985-0.996), with no significant bias observed between observers. Conclusions EZ width can be measured using LRPs with excellent repeatability and reproducibility. Our observation of greater HW than VW is consistent with previous observations in RP, though the reason for this anisotropy remains unclear. Translational Relevance We describe repeatability and reproducibility of a method for measuring EZ width in patients with RP or Usher syndrome. This approach could facilitate measurement of retinal band thickness and/or intensity.

Over 1 million HIV infections have been diagnosed in Russia, and HIV care uptake and viral suppression are very low. 241 HIV-positive individuals in St. Petersburg were enrolled through social networks, provided blood for viral load testing, and completed measures of medication-taking adherence, readiness, and self-efficacy; psychosocial well-being; and substance use. Outcomes included attending an HIV care appointment in the past 6 months, >90% ART adherence, and undetectable viral load. 26% of participants had no recent care appointment, 18% had suboptimal adherence, and 56% had detectable viral load. Alcohol use consistently predicted all adverse health outcomes. Having no recent care visit was additionally associated with being single and greater past-month drug injection frequency. Poor adherence was additionally predicted by lower medication-taking self-efficacy and lower anxiety. Detectable viral load was additionally related to younger age. Comprehensive interventions to improve HIV care in Russia must address substance abuse, anxiety, and medication-taking self-efficacy.

The aim of this study was to determine the tube-related complications and feeding outcomes of infants discharged home from the neonatal intensive care unit (NICU) with nasogastric (NG) tube feeding or gastrostomy (G-tube) feeding.We performed a chart review of 335 infants discharged from our NICU with home NG tube or G-tube feeding between January 2009 and December 2013. The primary outcome was the incidence of feeding tube-related complications requiring emergency department (ED) visits, hospitalizations, or deaths. Secondary outcome was feeding status at 6 months postdischarge. Univariate and multivariate analyses were conducted.There were 322 infants discharged with home enteral tube feeding (NG tube, n = 84; G-tube, n = 238), with available outpatient data for the 6-month postdischarge period. A total of 115 ED visits, 28 hospitalizations, and 2 deaths were due to a tube-related complication. The incidence of tube-related complications requiring an ED visit was significantly higher in the G-tube group compared with the NG tube group (33.6% vs 9.5%, P.001). Two patients died due to a G-tube-related complication. By 6 months postdischarge, full oral feeding was achieved in 71.4% of infants in the NG tube group compared with 19.3% in the G-tube group ( P.001). Type of feeding tube and percentage of oral feeding at discharge were significantly associated with continued tube feeding at 6 months postdischarge.Home NG tube feeding is associated with fewer ED visits for tube-related complications compared with home G-tube feeding. Some infants could benefit from a trial home NG tube feeding.

OBJECTIVE: To determine the degree to which preinjury and acute postinjury psychosocial and injury-related variables predict symptom duration following sport-related concussion. METHODS: A total of 2,055 high school and collegiate athletes completed preseason evaluations. Concussed athletes (n = 127) repeated assessments serially (

Sarcopenia describes a loss of muscle mass and resultant decrease in strength, mobility, and function that can be quantified by CT. We hypothesized that sarcopenia and related frailty characteristics are related to discharge disposition after blunt traumatic injury in the elderly. We reviewed charts of 252 elderly blunt trauma patients who underwent abdominal CT prior to hospital admission. Data for thirteen frailty characteristics were abstracted. Sarcopenia was measured by obtaining skeletal muscle cross-sectional area (CSA) from each patient’s psoas major muscle using Slice-O-Matic® software. Dispositions were grouped as dependent and independent based on discharge location. χ 2, Fisher’s exact, and logistic regression were used to determine factors associated with discharge dependence. Mean age 76 years, 49 % male, median ISS 9.0 (IQR = 8.0–17.0). Discharge destination was independent in 61.5 %, dependent in 29 %, and 9.5 % of patients died. Each 1 cm2 increase in psoas muscle CSA was associated with a 20 % decrease in dependent living (p

A sign-based (SB) approach suggests an alternative criterion for quantile regression fit. The SB criterion is a piecewise constant function, which often leads to a non-unique solution. We compare the mid-point of this SB solution with the least absolute deviations (LAD) method and describe asymptotic properties of SB estimators under a weaker set of assumptions as compared with the assumptions often used with the generalized method of moments. Asymptotic properties of LAD and SB estimators are equivalent; however, there are finite sample differences as we show in simulation studies. At small to moderate sample sizes, the SB procedure for modelling quantiles at longer tails demonstrates a substantially lower bias, variance, and mean-squared error when compared with the LAD. In the illustrative example, we model a 0.8-level quantile of hospital charges and highlight finite sample advantage of the SB versus LAD.

Background Despite documented benefits of cardiac rehabilitation, adherence to programs is suboptimal with an average dropout rate of between 24% and 50%. The goal of this study was to identify organizational and patient factors associated with cardiac rehabilitation adherence. Methods and Results Facilities of the W isconsin C ardiac R ehabilitation O utcomes R egistry Project (N=38) were surveyed and records of 4412 enrolled patients were analyzed. Generalized estimating equations were used to account for clustering of patients within facilities. The results show that organizational factors associated with significantly increased adherence were relaxation training and diet classes (group and individual formats) and group‐based psychological counseling, medication counseling, and lifestyle modification, the medical director's presence in the cardiac rehabilitation activity area for ≥15 min/week, assessment of patient satisfaction, adequate space, and adequate equipment. Patient factors associated with significantly increased adherence were aged ≥65 years, the A merican A ssociation of C ardiovascular and P ulmonary R ehabilitation ( AACVPR ) high‐risk category, having received coronary artery bypass grafting, and diabetes disease. Non‐white race was negatively associated with adherence. There was no significant gender difference in adherence. None of the baseline patient clinical profiles were associated with adherence including body mass index, total cholesterol, low‐density lipoprotein, high‐density lipoprotein, triglycerides, and blood pressure. Conclusions Factors associated with adherence to cardiac rehabilitation included both organizational and patient factors. Modifiable organizational factors may help directors of cardiac rehabilitation programs improve patient adherence to this beneficial program.

The Ponseti method is a widely accepted and highly successful conservative treatment of pediatric clubfoot involving weekly manipulations and cast applications. Qualitative assessments have indicated the potential success of the technique with cast materials other than standard plaster of Paris. However, guidelines for clubfoot correction based on the mechanical response of these materials have yet to be investigated. The current study sought to characterize and compare the ability of three standard cast materials to maintain the Ponseti-corrected foot position by evaluating cast creep response. A dynamic cast testing device, built to model clubfoot correction, was wrapped in plaster of Paris, semi-rigid fiberglass, and rigid fiberglass. Three-dimensional motion responses to two joint stiffnesses were recorded. Rotational creep displacement and linearity of the limb-cast composite were analyzed. Minimal change in position over time was found for all materials. Among cast materials, the rotational creep displacement was significantly different ( p < 0.0001). The most creep displacement occurred in the plaster of Paris (2.0°), then the semi-rigid fiberglass (1.0°), and then the rigid fiberglass (0.4°). Torque magnitude did not affect creep displacement response. Analysis of normalized rotation showed quasi-linear viscoelastic behavior. This study provided a mechanical evaluation of cast material performance as used for clubfoot correction. Creep displacement dependence on cast material and insensitivity to torque were discovered. This information may provide a quantitative and mechanical basis for future innovations for clubfoot care.

Background: Access to primary care could reduce use of more costly health care by uninsured individuals through prevention and early treatment. We analyzed data from a program providing free primary care to test this hypothesis. Methods: We compared emergency room (ER) visits and hospitalizations among uninsured, low-income adults who received immediate versus delayed access to a program providing free primary care, including labs, X-rays, and specialty consultation. We used surveys to identify ER visits and hospitalizations during the 12 months preceding and following program enrollment or wait list entry. Results: Hospitalizations decreased from the year before entry to the year following entry in participants with immediate and delayed (6.0% vs 8.8% decrease) access. ER use also decreased in both groups (11.2% vs 15.4%). Conclusions: Free primary care services and specialty consultation did not reduce use of more costly health care services during its first year. More prolonged availability of primary care might have greater impact.

Background: Gait changes in patients with hallux valgus, including altered kinematic and temporal-spatial parameters, have been documented in the literature. Although operative treatment can yield favorable clinical and radiographic results, restoration of normal gait in this population remains unclear. Segmental kinematic changes within the foot and ankle during ambulation after operative correction of hallux valgus have not been reported. The aim of this study was to analyze changes in multisegmental foot and ankle kinematics in patients who underwent operative correction of hallux valgus. Methods: A 15-camera Vicon Motion Analysis System was used to evaluate 24 feet in 19 patients with hallux valgus preoperatively and postoperatively. The Milwaukee Foot Model was used to characterize segmental kinematics and temporal-spatial parameters (TSPs). Preoperative and postoperative kinematics and TSPs were compared using paired nonparametric methods; comparisons with normative data were performed using unpaired nonparametric methods. Outcomes were evaluated using the SF-36 assessment tool. Results: Preoperatively, patients with hallux valgus showed significantly altered temporal-spatial and kinematic parameters. Postoperatively, kinematic analysis demonstrated restoration of hallux position to normal. Hallux valgus angles and intermetatarsal angles were significantly improved, and outcomes showed a significant increase in performance of physical activities. Temporal-spatial parameters and kinematics in the more proximal segments were not significantly changed postoperatively. Conclusion: Postoperative results demonstrated significant improvement in foot geometry and hallux kinematics in the coronal and transverse planes. However, the analysis did not identify restoration of proximal kinematics. Clinical Relevance: Further investigation is necessary to explore possible causes/clinical relevance and appropriate treatment interventions for the persistently altered kinematics.

Therapy-related myelodysplastic syndromes (t-MDSs) and acute myeloid leukemia (t-AML) have a poor prognosis with conventional therapy. Encouraging results are reported after allogeneic transplantation. We analyzed outcomes in 868 persons with t-AML (n = 545) or t-MDS (n = 323) receiving allogeneic transplants from 1990 to 2004. A myeloablative regimen was used for conditioning in 77%. Treatment-related mortality (TRM) and relapse were 41% (95% confidence interval [CI], 38-44) and 27% (24-30) at 1 year and 48% (44-51) and 31% (28-34) at 5 years, respectively. Disease-free (DFS) and overall survival (OS) were 32% (95% CI, 29-36) and 37% (34-41) at 1 year and 21% (18-24) and 22% (19-26) at 5 years, respectively. In multivariate analysis, 4 risk factors had adverse impacts on DFS and OS: (1) age older than 35 years; (2) poor-risk cytogenetics; (3) t-AML not in remission or advanced t-MDS; and (4) donor other than an HLA-identical sibling or a partially or well-matched unrelated donor. Five-year survival for subjects with none, 1, 2, 3, or 4 of these risk factors was 50% (95% CI, 38-61), 26% (20-31), 21% (16-26), 10% (5-15), and 4% (0-16), respectively (P < .001). These data permit a more precise prediction of outcome and identify subjects most likely to benefit from allogeneic transplantation.

We examined transplantation outcomes after a second HLA-matched sibling transplantation for primary (16%) or secondary (84%) graft failure in 166 patients with severe acquired aplastic anemia (AA). Two-thirds of these patients has a performance score < 90. In most cases (88%), the same donor was used for both transplants, for both transplantations, and 84% of the second transplantations used bone marrow grafts. We identified 2 prognostic factors: intertransplantation interval (surrogate for primary graft failure and early secondary graft failure) and performance status. Shorter intertransplantation interval (≤ 3 months) and poor performance score (< 90) at second transplantation were associated with high mortality. In patients with a performance score of 90% to 100%, the 8-year probability of overall survival (OS) after second transplantation ≤ 3 and > 3 months from first transplantation was 56% and 76%, respectively. The corresponding probabilities in patients with lower performance scores were 33% and 61%. The predominant cause of failure after second transplantation was nonengraftment (in 72 of 166 patients), most commonly in patients with primary or early secondary graft failure (51 of 72; 71%). Our data indicate that novel approaches, including conditioning regimens with greater immunosuppression, should be explored for these patients.

Recently, in a series of papers, a method based on pseudo-values has been proposed for direct regression modeling of the survival function, the restricted mean and cumulative incidence function with right censored data. The models, once the pseudo-values have been computed, can be fit using standard generalized estimating equation software. Here we present SAS macros and R functions to compute these pseudo-values. We illustrate the use of these routines and show how to obtain regression estimates for a study of bone marrow transplant patients.

We evaluated effects of graft transport time on outcomes after transplantation of 938 unrelated donor bone marrow (BM) or 507 peripheral blood progenitor cells (PBPC) in patients with acute or chronic leukemia and myelodysplastic syndrome (MDS). BM grafts were collected at 107 centers and PBPC, 89 centers. Median time from end of collection to infusion was 14 hours for BM and 15 hours for PBPC. Platelet recovery was less likely in BM recipients when the interval from end of collection to receipt at transplant center was ≥20 hours (odds ratio 0.47, P = .010) and when the interval from receipt to infusion was ≥6 hours (odds ratio 0.57, P = .001). Mortality rates were higher in recipients of HLA-matched BM when the interval from end of collection to receipt at transplant center was ≥20 hours (relative risk 2.67, P < .001) after adjustment for other significant prognostic factors. Mortality after HLA-mismatched BM transplants was not associated with transport time. Transport times had no demonstrable effect on outcomes after PBPC transplants. These data support a general review of current transport procedures, especially for BM grafts requiring longer transport time and every effort made to minimize time from collection to infusion.