Outcomes of Referrals in Pediatric Patients With Peripheral Lymphadenopathy.

Lymphadenopathy is a common reason for referral to a subspecialist, which may result in significant anxiety for parents. Understanding which patients require a subspecialty referral for lymphadenopathy is key to streamlining health care utilization for this common clinical entity. This is an IRB-approved retrospective study examining pediatric patients consecutively referred to pediatric hematology oncology, otolaryngology, or surgery for lymphadenopathy from 2012 to 2021 at a free-standing tertiary-care children's hospital. Logistic regression was fitted to examine the association between the maximum size of the lymph nodes (LN) and a diagnosis of malignancy. The odds ratio, area under the receiver operator curve, sensitivity, and specificity were estimated. We found a significant association between LN size and cancer diagnosis. For every centimeter increase in the maximal dimension of LN, there was an estimated 2.3 times increase in the odds of malignancy (OR=2.3, 95% CI: 1.65-3.11; P<0.0001). The estimated area under the curve (0.84, 95% CI: 0.78-0.90) indicated that LN size correlated well with cancer diagnosis. A LN cut-off size of 2 cm resulted in an estimated sensitivity of 1.0 (95% CI: 0.87-1.00) and specificity of 0.54 (95% CI: 0.46-0.61). Maximum LN size may be a predictor of malignancy among pediatric patients with lymphadenopathy.

Pediatric Ventilator Liberation: One-Hour Versus Two-Hour Spontaneous Breathing Trials in a Single Center.

BACKGROUND: The optimal spontaneous breathing trial (SBT) duration is not known for children who are critically ill. The study objective was to evaluate extubation outcomes between cohorts exposed to a 1- or 2-h SBT. METHODS: This was a retrospective cohort study of a quality improvement project database in a 24-bed pediatric ICU. The intervention was a respiratory therapist-driven SBT clinical pathway across 2 improvement cycles by using a 2- or 1-h SBT. The primary outcomes were extubation failure and rescue noninvasive ventilation in the first 48 h. Secondary outcomes included SBT results and process measures. RESULTS: There were 218 and 305 encounters in the 2- and 1-h cohorts, respectively. Extubation failure (7.3 vs 8.5%; P = .62) and rescue noninvasive ventilation rates (9.3 vs 8.2%; P = .68) were similar. In logistic regression models, SBT duration was not independently associated with either primary outcome. Extubation after 1-h SBT failure was associated with significantly higher odds of rescue noninvasive ventilation exposure (odds ratio 3.94, 95% CI 1.3-11.9; P = .02). SBT results were not associated with odds of extubation failure. There were 1,072 (2 h) and 1,333 (1 h) SBTs performed. The 1-h SBT pass rate was significantly higher versus the 2-h SBT (71.4 vs 51.1%; P < .001). Among all failed SBTs, the top 3 reported failure modes were tidal volume ≤ 5 mL/kg (23.6%), breathing frequency increase > 30% (21%), and oxygen saturation < 92% (17.3%). When considering all failed SBTs, 75.5% of failures occurred before 45 min. CONCLUSIONS: A 1-h SBT may be a viable alternative to a 2-h version for the average child who is critically ill. Further, a 1-h SBT may better balance extubation outcomes and duration of invasive ventilation for the general pediatric ICU population.

Risk factors for community acquired pediatric urinary tract infection with extended-spectrum-ß-lactamase Escherichia coli - A case-control study.

INTRODUCTION: Community-acquired (CA) infections caused by extended-spectrum ß-lactamase (ESBL) producing Escherichia coli urinary tract infections (UTI) have become increasingly prevalent, posing a serious threat to public health. Risk factors for ESBL UTI have not been extensively studied in the pediatric population. We report findings from a case control study to identify risk factors for CA ESBL-producing E. coli UTI in children. MATERIALS AND METHOD: A cohort of children with CA ESBL Escherichia coli UTI evaluated at a tertiary referral hospital from January 2014 through April 2021, were matched 1:3 with control group of non-ESBL CA E. coli UTI based on age at first episode of non-ESBL UTI. To identify potential risk factors for ESBL E. coli UTI, conditional logistic regression model was utilized accounting for age matching. Univariate models were fitted for each clinical risk factor. Factors found to be significantly associated with ESBL UTI were simultaneously included in a single model to check for associations adjusted for all other factors. RESULTS: On conditional multivariate analyses for univariate testing, male sex (P = 0.021), history of Urology care (P = 0.001), and antibiotic treatment within 30 days prior to positive culture (P = 0.004) were identified as independent risk factors for CA ESBL E. coli UTI. Comorbidity scores were assigned to each patient according to pediatric comorbidity index (PCI); children with ESBL UTI were more likely to have higher morbidity risk than non-ESBL UTI children (P < 0.001). From the logistic model, the higher the morbidity scores, the more likely children will have CA ESBL UTI (P < 0.001). DISCUSSION: Identifying risk factors for ESBL-producing E. coli UTI in children is important because of limited therapeutic options. This knowledge is essential for clinical decision making and to develop intervention strategies to reduce disease burden. Our study found that although females have an increased predisposition to UTIs, we observed that the male sex is an independent risk factor for ESBL E. coli UTI. This finding warrants further investigation to determine underlying cause. Because of the retrospective design of the study, collection of data from a single center, and differences in characteristics between patient populations, treatments, and prescribing patterns in the community, this study may not be generalizable. CONCLUSIONS: Findings from our case-control study suggest that the male sex, history of Urology care, and previous antibiotic exposure are independent risk factors for CA ESBL-GNB UTI. Children with ESBL E. coli UTI are more likely to have longer admission duration and higher comorbidity index.

Immune Activity and Response Differences of Oncolytic Viral Therapy in Recurrent Glioblastoma: Gene Expression Analyses of a Phase IB Study.

PURPOSE: Previously, clinical trials of experimental virotherapy for recurrent glioblastoma multiforme (GBM) demonstrated that inoculation with a conditionally replication-competent Δγ134.5 oncolytic herpes simplex virus (oHSV), G207, was safe. Following the initial safety study, a phase Ib trial enrolled 6 adult patients diagnosed with GBM recurrence from which tumor tissue was banked for future studies. PATIENTS AND METHODS: Here, we analyzed tumor RNA sequencing (RNA-seq) data obtained from pre- and posttreatment (collected 2 or 5 days after G207 injection) biopsies from the phase Ib study patients. RESULTS: Using a Spearman rank-order correlation analysis, we identified approximately 500 genes whose expression pattern correlated with survival duration. Many of these genes were enriched for the intrinsic IFN-mediated antiviral and adaptive immune functional responses, including immune cell chemotaxis and antigen presentation to T-cells. Furthermore, we show that the expression of several T-cell-related genes was highest in the patient with the longest survival after G207 inoculation. CONCLUSIONS: Our data support that the oHSV-induced type I IFN production and the subsequent recruitment of an adaptive immune response differed between enrolled patients and showed association with survival duration in patients with recurrent malignant glioma after treatment with an early generation oHSV.

Exploration of Sepsis-Associated Coagulopathy Severity and Pediatric Septic Shock Outcomes.

The objective of this study was to explore correlations between sepsis-associated coagulopathy (SAC) in pediatric septic shock and clinical outcomes. This was a retrospective cohort study of all children admitted to a single, academic pediatric intensive care unit with septic shock over 6 years. The prevalence of SAC was 93.5% with 61% being severe. Those with severe SAC were more likely to have a positive blood culture and have longer median duration of ventilation. All observed mortalities occurred in the severe SAC and indeterminate SAC groups. SAC is highly prevalent in pediatric septic shock and may predict important outcomes.

Diurnal Variation and Nursing Perspectives in Analgesic and Sedation Medication Administration to Mechanically Ventilated Children in a Single Pediatric ICU.

The primary objective of this study was to determine whether there was diurnal variation in the amount of analgesic and sedation medication administered to mechanically ventilated children in a single pediatric intensive care unit (PICU). The secondary objective was to evaluate nursing attitudes and practices regarding administration of these medications. This was a prospective, longitudinal cohort study of mechanically ventilated patients admitted to a single PICU. There were 46 mechanical ventilation courses included (305 paired day-night shifts). There was no significant diurnal variation found in the amount of analgesics and sedatives administered to mechanically ventilated patients. However, the reasons for administration differed between day and night shifts.

Minimal manifestation status and prednisone withdrawal in the MGTX trial.

OBJECTIVE: To examine whether sustained minimal manifestation status (MMS) with complete withdrawal of prednisone is better achieved in thymectomized patients with myasthenia gravis (MG). METHODS: This study is a post hoc analysis of data from a randomized trial of thymectomy in MG (Thymectomy Trial in Non-Thymomatous Myasthenia Gravis Patients Receiving Prednisone Therapy [MGTX]). MGTX was a multicenter, randomized, rater-blinded 3-year trial that was followed by a voluntary 2-year extension for patients with acetylcholine receptor (AChR) antibody-positive MG without thymoma. Patients were randomized 1:1 to thymectomy plus prednisone vs prednisone alone. Participants were age 18-65 years at enrollment with disease duration less than 5 years. All patients received oral prednisone titrated up to 100 mg on alternate days until they achieved MMS, which prompted a standardized prednisone taper as long as MMS was maintained. The achievement rate of sustained MMS (no symptoms of MG for 6 months) with complete withdrawal of prednisone was compared between the thymectomy plus prednisone and prednisone alone groups. RESULTS: Patients with MG in the thymectomy plus prednisone group achieved sustained MMS with complete withdrawal of prednisone more frequently (64% vs 38%) and quickly compared to the prednisone alone group (median time 30 months vs no median time achieved, p < 0.001) over the 5-year study period. Prednisone-associated adverse symptoms were more frequent in the prednisone alone group and distress level increased with higher doses of prednisone. CONCLUSIONS: Thymectomy benefits patients with MG by increasing the likelihood of achieving sustained MMS with complete withdrawal of prednisone. CLINICALTRIALSGOV IDENTIFIER: NCT00294658. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for patients with generalized MG with AChR antibody, those receiving thymectomy plus prednisone are more likely to attain sustained MMS and complete prednisone withdrawal than those on prednisone alone.

Functional outcomes at 2 years of age following treatment for posthemorrhagic hydrocephalus of prematurity: what do we know at the time of consult?

OBJECTIVE: Posthemorrhagic hydrocephalus of prematurity remains a significant problem in preterm infants. In the literature, there is a scarcity of data on the early disease process, when neurosurgeons are typically consulted for recommendations on treatment. Here, the authors sought to evaluate functional outcomes in premature infants at 2 years of age following treatment for posthemorrhagic hydrocephalus. Their goal was to determine the relationship between factors identifiable at the time of the initial neurosurgical consult and outcomes of patients when they are 2 years of age. METHODS: The authors performed a retrospective chart review of premature infants treated for intraventricular hemorrhage (IVH) of prematurity (grade III and IV) between 2003 and 2014. Information from three time points (birth, first neurosurgical consult, and 2 years of age) was collected on each patient. Logistic regression analysis was performed to determine the association between variables known at the time of the first neurosurgical consult and each of the outcome variables. RESULTS: One hundred thirty patients were selected for analysis. At 2 years of age, 16% of the patients had died, 88% had cerebral palsy/developmental delay (CP), 48% were nonverbal, 55% were nonambulatory, 33% had epilepsy, and 41% had visual impairment. In the logistic regression analysis, IVH grade was an independent predictor of CP (p = 0.004), which had an estimated probability of occurrence of 74% in grade III and 96% in grade IV. Sepsis at or before the time of consult was an independent predictor of visual impairment (p = 0.024), which had an estimated probability of 58%. IVH grade was an independent predictor of epilepsy (p = 0.026), which had an estimated probability of 18% in grade III and 43% in grade IV. The IVH grade was also an independent predictor of verbal function (p = 0.007), which had an estimated probability of 68% in grade III versus 41% in grade IV. A higher weeks gestational age (WGA) at birth was an independent predictor of the ability to ambulate (p = 0.0014), which had an estimated probability of 15% at 22 WGA and up to 98% at 36 WGA. The need for oscillating ventilation at consult was an independent predictor of death before 2 years of age (p = 0.001), which had an estimated probability of 42% in patients needing oscillating ventilation versus 13% in those who did not. CONCLUSIONS: IVH grade was consistently an independent predictor of functional outcomes at 2 years. Gestational age at birth, sepsis, and the need for oscillating ventilation may also predict worse functional outcomes.

Employment in refractory myasthenia gravis: A Myasthenia Gravis Foundation of America Registry analysis.

INTRODUCTION: Labor-market participation is potentially very difficult for patients with refractory myasthenia gravis (MG). In this study, employment status and work absences are compared between refractory and nonrefractory MG. METHODS: Adults (aged 18-64 years, all diagnosed ≥2 years previously) were included if enrolled in the Myasthenia Gravis Foundation of America Patient Registry during July 2013 to February 2018. RESULTS: Seventy-six patients (9.2%) had refractory and 749 (90.8%) had nonrefractory disease; demographic data did not differ between groups. Relative to the nonrefractory group, the refractory group patients were more than twice as likely to work fewer hours per week (odds ratio [95% confidence interval]: currently employed, 2.777 [1.640-4.704]; employed over previous 6 months, 2.643 [1.595-4.380]), but those employed were not more likely to be absent from work. DISCUSSION: Because absence from the labor market adversely affects quality of life and personal finances, these findings reaffirm the considerable disease burden associated with refractory MG.

Examining the Impact of Refractory Myasthenia Gravis on Healthcare Resource Utilization in the United States: Analysis of a Myasthenia Gravis Foundation of America Patient Registry Sample.

BACKGROUND AND PURPOSE: Patients with refractory myasthenia gravis (MG) experience ongoing disease burden that might be reflected in their healthcare utilization. Here we examine the impact of refractory MG on healthcare utilization. METHODS: The 825 included participants were aged 18-64 years, enrolled in the Myasthenia Gravis Foundation of America Patient Registry between July 2013 and February 2018, and had been diagnosed with MG ≥2 years previously. RESULTS: Participants comprised 76 (9.2%) with refractory MG and 749 (90.8%) with nonrefractory MG. During the 6 months before enrollment, participants with refractory MG were significantly more likely than those with nonrefractory MG to have experienced at least one exacerbation [67.1% vs. 52.0%, respectively, p=0.01; odds ratio (OR)=1.882, 95% confidence interval (CI)=1.141-3.104], visited an emergency room at least once [43.4% vs. 27.1%, p<0.01; OR=2.065, 95% CI=1.276-3.343], been hospitalized overnight at least once (32.9% vs. 20.5%, p=0.01; OR=1.900, 95% CI=1.140-3.165), ever been admitted to an intensive care unit (ICU) (61.8% vs. 33.4%, p<0.01; OR=3.233, 95% CI=1.985-5.266), or ever required a feeding tube (21.1% vs. 9.1%, p<0.01; OR=2.671, 95% CI=1.457-4.896). A total of 75.8% younger females with refractory disease (<51 years, n=33) experienced at least one exacerbation, 69.7% had been admitted to an ICU, and 30.3% had required a feeding tube. For older females with refractory disease (≥51 years, n=33), 60.6%, 54.6%, and 6.1% experienced these outcomes, respectively (between-group differences were not significant). CONCLUSIONS: Refractory MG is associated with higher disease burden and healthcare utilization than nonrefractory MG.

Predictors of Hospital Reuse Among Publicly Insured Children Hospitalized for Status Asthmaticus.

BACKGROUND: Asthma is a common cause of pediatric hospitalization. Nonadherence to asthma medications is associated with worse outcomes; however, there is a paucity of data regarding posthospitalization prescription filling and hospital reuse. Our objective was to identify patients at risk for hospital reuse after being hospitalized for asthma. METHODS: This is a retrospective study of patients with asthma who were discharged from a children's hospital in which we use Medicaid claims data to evaluate prescription fills within 30 days and 12 months. Chart reviews were used for demographics, chronic asthma severity, admission severity, and hospital reuse. t and χ2 tests were performed for continuous and categorical variables. A generalized linear mixed model was fitted to predict the odds of hospital reuse, which was defined as requiring an emergency department visit or rehospitalization. Survival analysis using log-rank testing was used for modeling the time to hospital reuse. RESULTS: Fifty-four percent of patients discharged with asthma had hospital reuse within 1 year of discharge. There was no association between hospital reuse and prescription filling for systemic steroids (odds ratio [OR] 1.30; confidence interval [CI]: 0.85-2.00; P = .21) or controller medications (OR 1.5; CI: 0.92-2.52; P = .10). There was a higher number of controller and systemic steroid prescription fills over 12 months for patients with hospital reuse. The factors associated with greater odds of hospital reuse were severity of chronic asthma diagnosis (P = .03) as well as African American race (OR 1.92; CI: 1.17-3.13; P = .01). CONCLUSIONS: For Medicaid-insured patients discharged with asthma, worse chronic asthma severity and African American race were associated with greater odds of hospital reuse. Decreased prescription filling was not associated with greater odds of hospital reuse.

Long-term effect of thymectomy plus prednisone versus prednisone alone in patients with non-thymomatous myasthenia gravis: 2-year extension of the MGTX randomised trial.

BACKGROUND: The Thymectomy Trial in Non-Thymomatous Myasthenia Gravis Patients Receiving Prednisone (MGTX) showed that thymectomy combined with prednisone was superior to prednisone alone in improving clinical status as measured by the Quantitative Myasthenia Gravis (QMG) score in patients with generalised non-thymomatous myasthenia gravis at 3 years. We investigated the long-term effects of thymectomy up to 5 years on clinical status, medication requirements, and adverse events. METHODS: We did a rater-blinded 2-year extension study at 36 centres in 15 countries for all patients who completed the randomised controlled MGTX and were willing to participate. MGTX patients were aged 18 to 65 years at enrolment, had generalised non-thymomatous myasthenia gravis of less than 5 years' duration, had acetylcholine receptor antibody titres of 1·00 nmol/L or higher (or concentrations of 0·50-0·99 nmol/L if diagnosis was confirmed by positive edrophonium or abnormal repetitive nerve stimulation, or abnormal single fibre electromyography), had Myasthenia Gravis Foundation of America Clinical Classification Class II-IV disease, and were on optimal anticholinesterase therapy with or without oral corticosteroids. In MGTX, patients were randomly assigned (1:1) to either thymectomy plus prednisone or prednisone alone. All patients in both groups received oral prednisone at doses titrated up to 100 mg on alternate days until they achieved minimal manifestation status. The primary endpoints of the extension phase were the time-weighted means of the QMG score and alternate-day prednisone dose from month 0 to month 60. Analyses were by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00294658. It is closed to new participants, with follow-up completed. FINDINGS: Of the 111 patients who completed the 3-year MGTX, 68 (61%) entered the extension study between Sept 1, 2009, and Aug 26, 2015 (33 in the prednisone alone group and 35 in the prednisone plus thymectomy group). 50 (74%) patients completed the 60-month assessment, 24 in the prednisone alone group and 26 in the prednisone plus thymectomy group. At 5 years, patients in the thymectomy plus prednisone group had significantly lower time-weighted mean QMG scores (5·47 [SD 3·87] vs 9·34 [5·08]; p=0·0007) and mean alternate-day prednisone doses (24 mg [SD 21] vs 48 mg [29]; p=0·0002) than did those in the prednisone alone group. 14 (42%) of 33 patients in the prednisone group, and 12 (34%) of 35 in the thymectomy plus prednisone group, had at least one adverse event by month 60. No treatment-related deaths were reported during the extension phase. INTERPRETATION: At 5 years, thymectomy plus prednisone continues to confer benefits in patients with generalised non-thymomatous myasthenia gravis compared with prednisone alone. Although caution is appropriate when generalising our findings because of the small sample size of our study, they nevertheless provide further support for the benefits of thymectomy in patients with generalised non-thymomatous myasthenia gravis. FUNDING: National Institutes of Health, National Institute of Neurological Disorders and Stroke.

Venous thromboembolism following inpatient pediatric surgery: Analysis of 153,220 patients.

PURPOSE: To evaluate venous thromboembolism (VTE) rates and risk factors following inpatient pediatric surgery. METHODS: 153,220 inpatient pediatric surgical patients were selected from the 2012-2015 NSQIP-P database. Demographic and perioperative variables were documented. Primary outcome was VTE requiring treatment within 30 postoperative days. Secondary outcomes included length of stay (LOS) and 30-day mortality. Prediction models were generated using logistic regression. Mortality and time to VTE were assessed using Kaplan-Meier survival analysis. RESULTS: 305 patients (0.20%) developed 296 venous thromboses and 12 pulmonary emboli (3 cooccurrences). Median time to VTE was 9 days. Most VTEs (81%) occurred predischarge. Subspecialties with highest VTE rates were cardiothoracic (0.72%) and general surgery (0.28%). No differences were seen for elective vs. urgent/emergent procedures (p = 0.106). All-cause mortality VTE patients was 1.2% vs. 0.2% in patients without VTE (p < 0.001). After stratifying by American Society of Anesthesiologists (ASA) class, no mortality differences remained when ASA < 3. Preoperative, postoperative, and total LOSs were longer for patients with VTE (p < 0.001 for each). ASA ≥ 3, preoperative sepsis, ventilator dependence, enteral/parenteral feeding, steroid use, preoperative blood transfusion, gastrointestinal disease, hematologic disorders, operative time, and age were independent predictors (C-statistic = 0.83). CONCLUSIONS: Pediatric postsurgical patients have unique risk factors for developing VTE. LEVEL OF EVIDENCE: Level II.

An introduction to Mendelian randomization with applications in neurology.

Mendelian randomization studies have become increasingly common due to the maturation of genome-wide association studies and its potential to ascertain causal relationships. With the increasing use of this method comes the need for medical practitioners and clinicians to develop an understanding of its rationale, limitations, and interpretation. Mendelian randomization attempts to ascertain a causal relationship between some risk factor of interest and some outcome or disease of interest. It exploits Mendel's law on the random assortment of genetic variants. This random assortment of genetic variants mimics the main principle of randomization used in clinical trials; with the genetic variant replacing the randomly allocated treatment. In this paper we provide a readable introduction to the rationale behind Mendelian randomization and its limitations. We also discuss and interpret several examples of Mendelian randomization analyses which pertain to neurological diseases.

Histopathology of thymectomy specimens from the MGTX-trial: Entropy analysis as strategy to quantify spatial heterogeneity of lymphoid follicle and fat distribution.

The thymectomy specimens from the "thymectomy trial in non-thymomatous myasthenia gravis patients receiving prednisone therapy" (MGTX) underwent rigid and comprehensive work-up, which permits analysis of the spatial distribution of histological and immunohistological features. This analysis revealed strong intra- and inter-case variability. While many histological features (e.g. median percent fat content among different specimens) can easily be correlated with clinical parameters, intra-case spatial variability of histological features has yet defied quantification and statistical evaluation. To overcome this gap in digital pathology, we here propose intra-case entropy of measured histological features in all available slides of a given thymectomy specimen as a quantitative marker of spatial histological heterogeneity. Calculation of entropy led to one value per specimen and histological feature. Through these 'entropy values' the so far neglected degree of spatial histological heterogeneity could be fed into statistical analyses, extending the scope of clinico-pathological correlations.

Similar clinical benefits from below-target and target dose enalapril in patients with heart failure in the SOLVD Treatment trial.

AIMS: To examine associations of below-target and target dose of enalapril, an angiotensin-converting enzyme (ACE) inhibitor, with outcomes in patients with heart failure and reduced ejection fraction (HFrEF) in the Studies of Left Ventricular Dysfunction (SOLVD) Treatment trial. METHODS AND RESULTS: Two thousand five hundred and sixty-nine patients with HFrEF (ejection fraction ≤35%) were randomized to below-target (5-10 mg/day) dose placebo (n = 1284) or enalapril (n = 1285). One month post-randomization, blind up-titration to target (20 mg/day) dose was attempted for both study drugs in 2458 patients. Among the 1444 patients who achieved dose up-titration (placebo, n = 748; enalapril, n = 696; mean dose for both groups, 20.0 mg/day), target dose enalapril (vs. target dose placebo) was associated with a 9% absolute lower risk of the combined endpoint of heart failure hospitalization or all-cause mortality [adjusted hazard ratio (HR) 0.70; 95% confidence interval (CI) 0.60-0.81; P < 0.001] during 4 years of follow-up. Among the 1014 patients who could not achieve target dose (placebo, n = 486; enalapril, n = 528; mean dose for both groups, 8.8 mg/day), below-target dose enalapril (vs. below-target dose placebo) was associated with a 12% absolute lower risk of the combined endpoint of heart failure hospitalization or all-cause mortality (adjusted HR 0.68; 95% CI 0.57-0.81; P < 0.001). Among the 1224 patients receiving enalapril, target (vs. below-target) dose had no association with the combined endpoint of heart failure hospitalization or all-cause mortality (adjusted HR 1.04; 95% CI 0.87-1.23; P = 0.695). CONCLUSION: In patients with HFrEF, the clinical benefits of ACE inhibitors appear to be similar at both below-target and target doses.

A tool to visualize and analyze perfusion data: Development and application of the R package "CTP".

BACKGROUND AND OBJECTIVE: Computed tomography perfusion (CTP) is a widely used imaging modality especially in neuroimaging. Despite this, CTP is often prohibitive due to the dearth of free/open-source software. This could have wide-ranging implications for instruction and research. We have implemented an online-available CTP tool built and run completely within the R computing environment. METHODS: Called from within R, the user can select one of four different methods to construct a cerebral blood flow (CBF) map: (1) max-slope (2) singular value decomposition (3) block circulant singular value decomposition or (4) oscillation minimization singular value decomposition. The four methods are compared against a digital CBF phantom. RESULTS: All four methods generate a CBF map, with the oscillation minimization technique giving the most accurate map. CONCLUSIONS: We have constructed an easily accessible teaching and research tool to create a CBF map and made it freely available. We hope this tool will help facilitate understanding of the methods involved in constructing perfusion maps and be a valuable resource to future researchers.

The Epidemiology of Healthcare-associated Infections in Pediatric Cardiac Intensive Care Units.

BACKGROUND: Healthcare-associated infections (HAIs) represent serious complications for patients within pediatric cardiac intensive care units (CICU). HAIs are associated with increased morbidity, mortality and resource utilization. There are few studies describing the epidemiology of HAIs across the entire spectrum of patients (surgical and nonsurgical) receiving care in dedicated pediatric CICUs. METHODS: Retrospective analyses of 22,839 CICU encounters from October 2013 to September 2016 across 22 North American CICUs contributing data to the Pediatric Cardiac Critical Care Consortium clinical registry. RESULTS: HAIs occurred in 2.4% of CICU encounters at a rate of 3.3 HAIs/1000 CICU days, with 73% of HAIs occurring in children <1 year. Eighty encounters (14%) had ≥2 HAIs. Aggregate rates for the 4 primary HAIs are as follows: central line-associated blood stream infection, 1.1/1000 line days; catheter-associated urinary tract infections, 1.5/1000 catheter days; ventilator-associated pneumonia, 1.9/1000 ventilator days; surgical site infections, 0.81/100 operations. Surgical and nonsurgical patients had similar HAIs rates/1000 CICU days. Incidence was twice as high in surgical encounters and increased with surgical complexity; postoperative infection occurred in 2.8% of encounters. Prematurity, younger age, presence of congenital anomaly, Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery Congenital Heart Surgery Mortality Categories (STAT) 4-5 surgery, admission with an active medical condition, open sternum and extracorporeal membrane oxygenation were independently associated with HAIs. In univariable analysis, HAI was associated with longer hospital length of stay and durations of urinary catheter, central venous catheter and ventilation. Mortality was 24.4% in patients with HAIs versus 3.4% in those without, P < 0.0001. CONCLUSIONS: We provide comprehensive multicenter benchmark data regarding rates of HAIs within dedicated pediatric CICUs. We confirm that although rare, HAIs of all types are associated with significant resource utilization and mortality.

Randomized Trial of Thymectomy in Myasthenia Gravis.

BACKGROUND: Thymectomy has been a mainstay in the treatment of myasthenia gravis, but there is no conclusive evidence of its benefit. We conducted a multicenter, randomized trial comparing thymectomy plus prednisone with prednisone alone. METHODS: We compared extended transsternal thymectomy plus alternate-day prednisone with alternate-day prednisone alone. Patients 18 to 65 years of age who had generalized nonthymomatous myasthenia gravis with a disease duration of less than 5 years were included if they had Myasthenia Gravis Foundation of America clinical class II to IV disease (on a scale from I to V, with higher classes indicating more severe disease) and elevated circulating concentrations of acetylcholine-receptor antibody. The primary outcomes were the time-weighted average Quantitative Myasthenia Gravis score (on a scale from 0 to 39, with higher scores indicating more severe disease) over a 3-year period, as assessed by means of blinded rating, and the time-weighted average required dose of prednisone over a 3-year period. RESULTS: A total of 126 patients underwent randomization between 2006 and 2012 at 36 sites. Patients who underwent thymectomy had a lower time-weighted average Quantitative Myasthenia Gravis score over a 3-year period than those who received prednisone alone (6.15 vs. 8.99, P<0.001); patients in the thymectomy group also had a lower average requirement for alternate-day prednisone (44 mg vs. 60 mg, P<0.001). Fewer patients in the thymectomy group than in the prednisone-only group required immunosuppression with azathioprine (17% vs. 48%, P<0.001) or were hospitalized for exacerbations (9% vs. 37%, P<0.001). The number of patients with treatment-associated complications did not differ significantly between groups (P=0.73), but patients in the thymectomy group had fewer treatment-associated symptoms related to immunosuppressive medications (P<0.001) and lower distress levels related to symptoms (P=0.003). CONCLUSIONS: Thymectomy improved clinical outcomes over a 3-year period in patients with nonthymomatous myasthenia gravis. (Funded by the National Institute of Neurological Disorders and Stroke and others; MGTX ClinicalTrials.gov number, NCT00294658.).