Gender-Specific Risk Factors for Reflux Esophagitis in a Predominantly Hispanic Population of a Large Safety-Net Hospital.

BACKGROUND: Defining factors associated with severe reflux esophagitis allows for identification of subgroups most at risk for complications of strictures and esophageal malignancy. We hypothesized there might be unique clinical features in patients with reflux esophagitis in a predominantly Hispanic population of a large, safety-net hospital. AIM: Define clinical and endoscopic features of reflux esophagitis in a predominantly Hispanic population of a large, safety-net hospital. METHODS: This is retrospective comparative study of outpatients and hospitalized patients identified with mild (Los Angeles Grade A/B) and severe (Los Angeles Grade C/D) esophagitis through an endoscopy database review. The electronic medical record was reviewed for demographic and clinical data. RESULTS: Reflux esophagitis was identified in 382/5925 individuals: 56.5% males and 79.8% Hispanic. Multivariable logistic regression model adjusted for age, gender, race, body mass index (BMI), tobacco and alcohol use, and hospitalization status with severity as the outcome showed an interaction between gender and BMI (p ≤ 0.01). Stratification by gender showed that obese females had decreased odds of severe esophagitis compared to normal BMI females (OR = 0.18, 95% CI = 0.07-0.47; p < 0.01). In males, the odds of esophagitis were higher in inpatient status (OR = 2.84, 95% CI = 1.52 - 5.28; p < 0.01) and as age increased (OR = 1.37, 95% CI = 1.03 - 1.83; p = 0.03). CONCLUSIONS: We identify gender-specific associations with severe esophagitis in a predominantly Hispanic cohort. In females, obese BMI appears to be protective against severe esophagitis compared to normal BMI, while in men inpatient status and increasing age were associated with increased odds of severe esophagitis.

The Efficacy of Platelet-Rich Plasma for Improving Pain and Function in Lateral Epicondylitis: A Systematic Review and Meta-analysis with Risk-of-Bias Assessment.

PURPOSE: To assess the efficacy of platelet-rich plasma (PRP) for lateral epicondylitis and evaluate its impact on pain and functional outcomes. METHODS: This study followed Preferred Reporting Items and Systematic Reviews and Meta-Analyses guidelines. A comprehensive literature search was conducted in September 2019 and repeated in April 2020 using electronic databases PubMed, MEDLINE, and the Cochrane Library. Baseline and 3-, 6-, and 12-month data were extracted for visual analog scale (VAS), Disabilities of the Arm, Shoulder, and Hand (DASH), and modified Mayo Clinic performance index for the elbow (MAYO) scores. Only level 1 studies with patients who had not undergone surgery were included. Outcomes data, study design, demographic variables, PRP formulation, and comparator treatments were recorded. Statistical analyses of pooled weighted mean differences (WMDs) were performed and compared with estimated minimal clinically important difference (MCID) values. The Coleman Methodology Score (CMS) was used to assess methodological quality, and the Cochrane risk-of-bias assessment was performed. RESULTS: This review included 16 level I studies, 9 of which (581 total patients, 281 receiving single injections of PRP) were quantitatively analyzed. The average age was 41.5 years, 56.8% of patients were female, and mean follow-up was 7.5 months. The mean CMS was 78.94 ± 12.74 (range 59 to 97), and 5 of 16 studies were at low risk for bias. Patients who received PRP had significantly improved VAS scores at 3 months (WMD -0.85; 95% confidence interval [CI] -1.03, -0.66; P < .01) and 6 months (WMD -0.74; 95% CI -0.98, -0.50; P < .01) compared with those who received autologous whole blood, though MAYO scores were statistically equivalent. Comparing PRP to corticosteroids, VAS and DASH scores were not significantly different at 3 months, although PRP was superior at 6 months for VAS (WMD -1.70; 95% CI -2.65, -0.75; P < .01) and DASH (WMD -6.23; 95% CI -10.78, -1.69; P < .01). Most differences in VAS and DASH scores exceeded the 5% absolute difference estimate for their respective MCIDs but fell short of the 10% estimate. CONCLUSION: Considering the small number of comparable studies, lack of quantification of specific PRP content, considerable heterogeneity between randomized control trials, and most effect sizes being equivocal within the framework of 2 estimated MCID values, the authors can neither scientifically support nor discourage the usage of PRP for lateral epicondylitis despite finding statistically significant improvements in pain and functional outcomes. LEVEL OF EVIDENCE: I, prognostic.

Use of Platelet-Rich Plasma for the Improvement of Pain and Function in Rotator Cuff Tears: A Systematic Review and Meta-analysis With Bias Assessment.

BACKGROUND: Many clinical trials have investigated the use of platelet-rich plasma (PRP) to treat rotator cuff-related abnormalities. Several meta-analyses have been published, but none have focused exclusively on level 1 randomized controlled trials. PURPOSE: To assess the efficacy of PRP for rotator cuff-related abnormalities and evaluate how specific tendon involvement, the inclusion of leukocytes, and the use of gel/nongel formulations affect pain and functional outcomes. STUDY DESIGN: Systematic review and meta-analysis. METHODS: The literature was screened following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Baseline, short-term, and long-term data were extracted for the Constant score, University of California, Los Angeles (UCLA) score, visual analog scale (VAS) for pain, retear rate, Simple Shoulder Test (SST), and American Shoulder and Elbow Surgeons (ASES) score. The 100-point modified Coleman Methodology Score (CMS) was used to assess methodological quality. Funnel plots and the Egger test were used to screen for publication bias, and sensitivity analysis was performed to evaluate the effect of potential outliers. RESULTS: A total of 18 level 1 studies were included in this review, 17 (1116 patients) of which could be included in quantitative analysis. The mean modified CMS was 79.4 ± 10.39. The Constant scores of patients who received PRP were significantly better short term (weighted mean difference [WMD], 2.89 [95% CI, 0.89-4.90]; P < .01) and long term (WMD, 2.66 [95% CI, 1.13-4.19]; P < .01). The VAS scores were significantly improved short term (WMD, -0.45 [95% CI, -0.75 to -0.15]; P < .01). Sugaya grade IV and V retears in PRP-treated patients were significantly reduced long term (odds ratio [OR], 0.34 [95% CI, 0.20-0.57]; P < .01). In PRP-treated patients with multiple tendons torn, there were reduced odds of retears (OR, 0.28 [95% CI, 0.13-0.60]; P < .01). Patients who received leukocyte-rich PRP had significantly better Constant scores compared with the leukocyte-poor PRP group, but there was no difference in VAS scores. Patients receiving PRP gel reported higher Constant scores compared with the controls, whereas those receiving nongel PRP treatments did not, although there was no difference in VAS scores. Long-term odds of retears were decreased, regardless of leukocyte content (leukocyte-poor PRP: OR, 0.36 [95% CI, 0.16-0.82]; leukocyte-rich PRP: OR, 0.32 [95% CI, 0.16-0.65]; all P < .05) or usage of gel (nongel: OR, 0.42 [95% CI, 0.23-0.76]; gel: OR, 0.17 [95% CI, 0.05-0.51]; all P < .01). CONCLUSION: Long-term retear rates were significantly decreased in patients with rotator cuff-related abnormalities who received PRP. Significant improvements in PRP-treated patients were noted for multiple functional outcomes, but none reached their respective minimal clinically important differences. Overall, our results suggest that PRP may positively affect clinical outcomes, but limited data, study heterogeneity, and poor methodological quality hinder firm conclusions.

Parenteral nutrition prolongs hospital stay in children with nonoperative blunt pancreatic injury: A propensity score weighted analysis.

BACKGROUND: Blunt pancreatic injury is frequently managed nonoperatively in children. Nutritional support practices - either enteral or parenteral - are heterogeneous and lack evidence-based guidelines. We hypothesized that use of parenteral nutrition (PN) in children with nonoperatively managed blunt pancreatic injury would 1) be associated with longer hospital stay and more frequent complications, and 2) differ in frequency by trauma center type. METHODS: We conducted a retrospective cohort study using the National Trauma Data Bank (2007-2016). Children (≤18 years) with blunt pancreatic injury were included. Patients were excluded for duodenal injury, mortality <4 days from admission, or laparotomy. We compared children that received versus those that did not receive PN. Logistic regression was used to model patient characteristics, injury severity, and trauma center type as predictors for propensity to receive PN. Treatment groups were balanced using the inverse probability of treatment weights. Outcomes included hospital length of stay, intensive care unit days, incidence of complications and mortality. RESULTS: 554 children with blunt pancreatic injury were analyzed. PN use declined in adult centers from 2012 to 2016, but remained relatively stable in pediatric centers. Propensity-weighted analysis demonstrated longer median length of stay in patients receiving PN (14 versus 4 days, rate ratio 2.19 [95% CI: 1.97, 2.43]). Children receiving PN also had longer ICU stay (rate ratio 1.73 [95% CI: 1.30, 2.30]). There was no significant difference in incidence of complications or mortality. CONCLUSIONS: Use of PN in children with blunt pancreatic injury that are managed nonoperatively differs between adult and pediatric trauma centers, and is associated with longer hospital stay. Early enteral feeding should be attempted first, with PN reserved for children with prolonged intolerance to enteral feeds. LEVEL OF EVIDENCE: III, Retrospective cohort.

EAST multicenter trial of simulation-based team training for pediatric trauma: Resuscitation task completion is highly variable during simulated traumatic brain injury resuscitation.

BACKGROUND: Best practices for benchmarking the efficacy of simulation-based training programs are not well defined. This study sought to assess feasibility of standardized data collection with multicenter implementation of simulation-based training, and to characterize variability in pediatric trauma resuscitation task completion associated with program characteristics. METHODS: A prospective multicenter observational cohort of resuscitation teams (N = 30) was used to measure task completion and teamwork during simulated resuscitation of a child with traumatic brain injury. A survey was used to measure center-specific trauma volume and simulation-based training program characteristics among participating centers. RESULTS: No task was consistently performed across all centers. Teamwork skills were associated with faster time to computed tomography notification (r = -0.51, p < 0.01). Notification of the operating room by the resuscitation team occurred more frequently in in situ simulation than in laboratory-based simulation (13/22 versus 0/8, p < 0.01). CONCLUSIONS: Multicenter implementation of a standardized pediatric trauma resuscitation simulation scenario is feasible. Standardized data collection showed wide variability in simulated resuscitation task completion.

A Phase II randomized controlled trial for lung and diaphragm protective ventilation (Real-time Effort Driven VENTilator management).

Lung Protective Mechanical Ventilation (MV) of critically ill adults and children is lifesaving but it may decrease diaphragm contraction and promote Ventilator Induced Diaphragm Dysfunction (VIDD). An ideal MV strategy would balance lung and diaphragm protection. Building off a Phase I pilot study, we are conducting a Phase II controlled clinical trial that seeks to understand the evolution of VIDD in critically ill children and test whether a novel computer-based approach (Real-time Effort Driven ventilator management (REDvent)) can balance lung and diaphragm protective ventilation to reduce time on MV. REDvent systematically adjusts PEEP, FiO2, inspiratory pressure, tidal volume and rate, and uses real-time measures from esophageal manometry to target normal levels of patient effort of breathing. This trial targets 276 children with pulmonary parenchymal disease. Patients are randomized to REDvent vs. usual care for the acute phase of MV (intubation to first Spontaneous Breathing Trial (SBT)). Patients in either group who fail their first SBT will be randomized to REDvent vs usual care for weaning phase management (interval from first SBT to passing SBT). The primary clinical outcome is length of weaning, with several mechanistic outcomes. Upon completion, this study will provide important information on the pathogenesis and timing of VIDD during MV in children and whether this computerized protocol targeting lung and diaphragm protection can lead to improvement in intermediate clinical outcomes. This will form the basis for a larger, Phase III multi-center study, powered for key clinical outcomes such as 28-day ventilator free days. Clinical Trials Registration: NCT03266016.

Timing of tracheostomy placement among children with severe traumatic brain injury: A propensity-matched analysis.

BACKGROUND: Early tracheostomy has been associated with shorter hospital stay and fewer complications in adult trauma patients. Guidelines for tracheostomy have not been established for children with severe traumatic brain injury (TBI). The purpose of this study was to (1) define nationwide trends in time to extubation and time to tracheostomy and (2) determine if early tracheostomy is associated with decreased length of stay and fewer complications in children with severe TBI. METHODS: Records of children (<15 years) with severe TBI (head Abbreviated Injury Severity [AIS] score ≥3) who were mechanically ventilated (>48 hours) were obtained from the National Trauma Data Bank (2007-2015). Outcomes after early (≤14 days) and late (≥15 days) tracheostomy placement were compared using 1:1 propensity score matching to control for potential confounding by indication. Propensity scores were calculated based on age, race, pulse, blood pressure, Glasgow Coma Scale motor score, injury mechanism, associated injury Abbreviated Injury Severity scores, TBI subtype, craniotomy, and intracranial pressure monitor placement. RESULTS: Among 6,101 children with severe TBI, 5,740 (94%) were extubated or died without tracheostomy, 95% of the time within 18 days. Tracheostomy was performed in 361 children (6%) at a median [interquartile range] of 15 [10, 22] days. Using propensity score matching, we compared 121 matched pairs with early or late tracheostomy. Early tracheostomy was associated with fewer ventilator days (14 [9, 19] vs. 25 [19, 35]), intensive care unit days (19 [14, 25] vs. 31 [24, 43]), and hospital days (26 [19, 41] vs. 39 [31, 54], all p < 0.05). Pneumonia (24% vs. 41%), venous thromboembolism (3% vs. 13%), and decubitus ulcer (4% vs. 13%) occurred less frequently with early tracheostomy (p < 0.05). CONCLUSIONS: Early tracheostomy is associated with shorter hospital stay and fewer complications among children with severe TBI. Extubation without tracheostomy is rare beyond 18 days after injury. LEVEL OF EVIDENCE: Prognostic and epidemiological, retrospective comparative study, level III.

Reduced Upper Limb Recovery in Subcortical Stroke Patients With Small Prior Radiographic Stroke.

Background: Research imaging costs limit lesion-based analyses in already expensive large stroke rehabilitation trials. Despite the belief that lesion characteristics influence recovery and treatment response, prior studies have not sufficiently addressed whether lesion features are an important consideration in motor rehabilitation trial design. Objective: Using clinically-obtained neuroimaging, evaluate how lesion characteristics relate to upper extremity (UE) recovery and response to therapy in a large UE rehabilitation trial. Methods: We reviewed lesions from 297 participants with mild-moderate motor impairment in the Interdisciplinary Comprehensive Arm Rehabilitation Evaluation (ICARE) study and their association with motor recovery, measured by the UE Fugl-Meyer (UE-FM). Significant lesion features identified on correlational and bivariate analysis were further analyzed for associations with recovery and therapy response using longitudinal mixed models. Results: Prior radiographic stroke was associated with less recovery on UE-FM in participants with motor impairment from subsequent subcortical stroke (-5.8 points) and in the overall sample (-3.6 points), but not in participants with cortical or mixed lesions. Lesion volume was also associated with less recovery, particularly after subcortical stroke. Every decade increase in age was associated with 1 less point of recovery on UE-FM. Response to specific treatment regimens varied based on lesion characteristics. Subcortical stroke patients experienced slightly less recovery with higher doses of upper extremity task-oriented training. Participants with cortical or mixed lesions experienced more recovery with higher doses of usual and customary therapy. Other imaging features (leukoaraiosis, ischemic vs. hemorrhagic stroke) were not significant. Conclusions: ICARE clinical imaging revealed information useful for UE motor trial design: stratification of persons with and without prior radiographic stroke may be required in participants with subcortical stroke, the majority of motor rehabilitation trial participants. Most of the prior radiographic strokes were small and cortically-based, suggesting even minor prior brain injury remote to the acute stroke lesion may limit spontaneous and therapy-related recovery. Lesion location may be associated with response to different therapy regimens, but the effects are variable and of unclear significance.

The Efficacy of Platelet-Rich Plasma on Tendon and Ligament Healing: A Systematic Review and Meta-analysis With Bias Assessment.

BACKGROUND: There has been a surge in high-level studies investigating platelet-rich plasma (PRP) for tendon and ligament injuries. A number of meta-analyses have been published, but few studies have focused exclusively on tendon and ligament injuries. PURPOSE: To perform a meta-analysis assessing the ability of PRP to reduce pain in patients with tendon and ligament injuries. STUDY DESIGN: Systematic review and meta-analysis. METHODS: This study followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A comprehensive search of the literature was carried out in April 2017 using electronic databases PubMed, MEDLINE, and the Cochrane Library. Only level 1 studies were included. Platelet and leukocyte count, injection volume, kit used, participant age/sex, comparator, and activating agent used were recorded. The short-term and long-term efficacy of PRP was assessed using the visual analog scale (VAS) to measure pain intensity. Injury subgroups (rotator cuff, tendinopathy, anterior cruciate ligament, and lateral epicondylitis) were evaluated. Funnel plots and the Egger test were used to screen for publication bias, and sensitivity analysis was performed to evaluate the effect of potential outliers by removing studies one at a time. RESULTS: Thirty-seven articles were included in this review, 21 (1031 participants) of which could be included in the quantitative analysis. The majority of studies published investigated rotator cuff injuries (38.1%) or lateral epicondylitis (38.1%). Seventeen studies (844 participants) reported short-term VAS data, and 14 studies (771 participants) reported long-term VAS data. Overall, long-term follow-up results showed significantly less pain in the PRP group compared with the control group (weighted mean difference [WMD], -0.84; 95% CI, -1.23 to -0.44; P < .01). Patients treated with PRP for rotator cuff injuries (WMD, -0.53; 95% CI, -0.98 to -0.09; P = .02) and lateral epicondylitis (WMD, -1.39; 95% CI, -2.49 to -0.29; P = .01) reported significantly less pain in the long term. Substantial heterogeneity was reported at baseline ( I2 = 72.0%; P < .01), short-term follow-up ( I2 = 72.5%; P < .01), long-term follow-up ( I2 = 76.1%; P < .01), and overall ( I2 = 75.8%; P < .01). The funnel plot appeared to be asymmetric, with some missingness at the lower right portion of the plot suggesting possible publication bias. CONCLUSION: This review shows that PRP may reduce pain associated with lateral epicondylitis and rotator cuff injuries.

Timing of mortality in pediatric trauma patients: A National Trauma Data Bank analysis.

BACKGROUND/PURPOSE: The classic "trimodal" distribution of death has been described in adult patients, but the timing of mortality in injured children is not well understood. The purpose of this study was to define the temporal distribution of mortality in pediatric trauma patients. METHODS: A retrospective cohort of patients with mortality from the National Trauma Data Bank (2007-2014) was analyzed. Categorical comparison of 'dead on arrival', 'death in the emergency department', and early (≤24h) or late (>24h) inpatient death was performed. Secondary analyses included mortality by pediatric age, predictors of early mortality, and late complication rates. RESULTS: Children (N=5463 deaths) had earlier temporal distribution of death compared to adults (n=104,225 deaths), with 51% of children dead on arrival or in ED compared to 44% of adults (p<0.001). For patients surviving ED resuscitation, children and adolescents had a shorter median time to death than adults (1.2 d and 0.8 days versus 1.6 days, p<0.001). Older age, penetrating mechanism, bradycardia, hypotension, tube thoracostomy, and thoracotomy were associated with early mortality in children. CONCLUSIONS: Injured children have higher incidence of early mortality compared to adults. This suggests that injury prevention efforts and strategies for improving early resuscitation have potential to improve mortality after pediatric injury. LEVEL OF EVIDENCE: Level III: Retrospective cohort study.

Self-assessment of team performance using T-NOTECHS in simulated pediatric trauma resuscitation is not consistent with expert assessment.

BACKGROUND: The Trauma NOn-TECHnical Skills (T-NOTECHS) tool has been used to assess teamwork in trauma resuscitation, but its reliability and validity for self-assessment is unknown. Our purpose was to determine the reliability and validity of self-administered T-NOTECHS in pediatric trauma resuscitation. METHODS: Simulated in situ resuscitations were evaluated using T-NOTECHS in real time by experts and immediately afterwards by team members. Reliability was analyzed with linear-weighted kappa and intra-class correlation. T-NOTECHS scores were compared between expert (gold-standard) and self-assessment. RESULTS: Fifteen simulations were examined. T-NOTECHS scores were similar between self- and expert assessment for leadership. Self-assessment scores were higher than expert for the other domains and total composite score. Inter-rater reliability for total score was similar between the two groups, but differences were observed in the domains. CONCLUSIONS: Self-assessment is not interchangeable with expert rating when using T-NOTECHS. Future studies need to determine how self-assessment can be best utilized. LEVEL OF EVIDENCE: Studies of diagnostic accuracy - Level 2.

Stroke Lesions in a Large Upper Limb Rehabilitation Trial Cohort Rarely Match Lesions in Common Preclinical Models.

BACKGROUND: Stroke patients with mild-moderate upper extremity motor impairments and minimal sensory and cognitive deficits provide a useful model to study recovery and improve rehabilitation. Laboratory-based investigators use lesioning techniques for similar goals. OBJECTIVE: To determine whether stroke lesions in an upper extremity rehabilitation trial cohort match lesions from the preclinical stroke recovery models used to drive translational research. METHODS: Clinical neuroimages from 297 participants enrolled in the Interdisciplinary Comprehensive Arm Rehabilitation Evaluation (ICARE) study were reviewed. Images were characterized based on lesion type (ischemic or hemorrhagic), volume, vascular territory, depth (cortical gray matter, cortical white matter, subcortical), old strokes, and leukoaraiosis. Lesions were compared with those of preclinical stroke models commonly used to study upper limb recovery. RESULTS: Among the ischemic stroke participants, median infarct volume was 1.8 mL, with most lesions confined to subcortical structures (61%) including the anterior choroidal artery territory (30%) and the pons (23%). Of ICARE participants, <1% had lesions resembling proximal middle cerebral artery or surface vessel occlusion models. Preclinical models of subcortical white matter injury best resembled the ICARE population (33%). Intracranial hemorrhage participants had small (median 12.5 mL) lesions that best matched the capsular hematoma preclinical model. CONCLUSIONS: ICARE subjects are not representative of all stroke patients, but they represent a clinically and scientifically important subgroup. Compared with lesions in general stroke populations and widely studied animal models of recovery, ICARE participants had smaller, more subcortically based strokes. Improved preclinical-clinical translational efforts may require better alignment of lesions between preclinical and human stroke recovery models.

NOS1 methylation and carotid artery intima-media thickness in children.

BACKGROUND: Nitric oxide (NO) plays an important role in cardiovascular health by maintaining and regulating vascular tone and blood flow. Epigenetic regulation of NO synthase (NOS), the genes responsible for NO production, may affect cardiovascular disease, including the development of atherosclerosis in children. METHODS AND RESULTS: We measured percentage DNA methylation using bisulfite conversion and pyrosequencing assays on DNA from buccal cells provided by 377 participants of the Children's Health Study on whom carotid artery intima-media thickness (CIMT) measurements were also collected. We examined a total of 16 CpG loci located within NOS1, NOS2A, NOS3, ARG1, and ARG2 genes responsible for NO production. CIMT was measured using high-resolution B-mode carotid ultrasound. The association between percentage DNA methylation in ARG and NOS genes with CIMT was evaluated using linear regression adjusted for sex, ethnicity, body mass index, age at CIMT, town of residence, and experimental plate for pyrosequencing reactions. Differences in the association by ethnicity and ancestral group were also evaluated. For a 1% increase in average DNA methylation of NOS1, CIMT increased by 1.2 µm (P=0.02). This association was greater in Hispanic children of Native American descent (ß=2.3; P=0.004) than in non-Hispanic whites (ß=0.3; P=0.71) or Hispanic whites (ß=1.0; P=0.35). CONCLUSIONS: DNA methylation of NOS1 has a plausible role in atherogenesis through regulation of NO production, although ancestry may alter the magnitude of this association.