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.

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.).

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.

Lack of evidence of increased mortality among patients with atrial fibrillation taking digoxin: findings from post hoc propensity-matched analysis of the AFFIRM trial.

AIMS: Digoxin is recommended for long-term rate control in paroxysmal, persistent, and permanent atrial fibrillation (AF). While some analyses suggest an association of digoxin with a higher mortality in AF, the intrinsic nature of this association has not been examined in propensity-matched cohorts, which is the objective of the current study. METHODS AND RESULTS: In Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM), 4060 patients with paroxysmal and persistent AF were randomized to rate (n = 2027) vs. rhythm (n = 2033) control strategies. Of these, 1377 received digoxin as initial therapy and 1329 received no digoxin at baseline. Propensity scores for digoxin use were estimated for each of these 2706 patients and used to assemble a cohort of 878 pairs of patients receiving and not receiving digoxin, who were balanced on 59 baseline characteristics. Matched patients had a mean age of 70 years, 40% were women, and 11% non-white. During the 3.4 years of the mean follow-up, all-cause mortality occurred in 14 and 13% of matched patients receiving and not receiving digoxin, respectively [hazard ratio (HR) associated with digoxin use: 1.06; 95% confidence interval (CI): 0.83-1.37; P = 0.640]. Among matched patients, digoxin had no association with all-cause hospitalization (HR: 0.96; 95% CI: 0.85-1.09; P = 0.510) or incident non-fatal cardiac arrhythmias (HR: 0.90; 95% CI: 0.37-2.23; P = 0.827). Digoxin had no multivariable-adjusted or propensity score-adjusted associations with these outcomes in the pre-match cohort. CONCLUSIONS: In patients with paroxysmal and persistent AF, we found no evidence of increased mortality or hospitalization in those taking digoxin as baseline initial therapy.

The magnetic resonance imaging 'rule of five': predicting the occurrence of relapse.

BACKGROUND: Clinical intuition suggests that a sharp increase in the number of enhancing lesions should signal an increased risk of relapse. The 'rule of five' recommends that subjects exhibiting at least five lesions over the baseline level be referred for closer monitoring. This rule has been used as an informal safety criterion with limited formal evaluation. OBJECTIVE: The purpose of this study was to determine the best threshold for the rule and to demonstrate its predictive validity for risk of subsequent relapses for multiple sclerosis (MS) trials. METHODS: We used logistic regression modeling to apply the rule to patient data from a phase II clinical trial. Predictive validity was ascertained using rate ratios and receiver operating characteristic (ROC) curves. RESULTS: We found that, for these data, a threshold of five lesions over the baseline constituted the best definition of a threshold. Overall, 35% of subjects broke the rule at least once. Breaking the rule increased the odds of imminent relapse by a factor of 3.2 (95% confidence interval (CI): 1.8-5.5). CONCLUSION: Breaking the rule of five was found to be a significant predictor of an imminent relapse. Length of follow-up and the number of lesions discovered via magnetic resonance imaging (MRI) were also significant predictors of relapse.

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.

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.

Hyperuricaemia, chronic kidney disease, and outcomes in heart failure: potential mechanistic insights from epidemiological data.

AIM: To determine if the association between hyperuricaemia and poor outcomes in heart failure (HF) varies by chronic kidney disease (CKD). METHODS AND RESULTS: Of the 2645 systolic HF patients in the Beta-Blocker Evaluation of Survival Trial with data on baseline serum uric acid, 1422 had hyperuricaemia (uric acid ≥6 mg/dL for women and ≥8 mg/dL for men). Propensity scores for hyperuricaemia, estimated for each patient, were used to assemble a matched cohort of 630 pairs of patients with and without hyperuricaemia who were balanced on 75 baseline characteristics. Associations of hyperuricaemia with outcomes during 25 months of median follow-up were examined in all patients and in those with and without CKD (estimated glomerular filtration rate of <60 mL/min/1.73 m(2)). Hyperuricaemia-associated hazard ratios (HRs) and 95% confidence intervals (CI) for all-cause mortality and HF hospitalization were 1.44 (1.12-1.85, P = 0.005) and 1.27 (1.02-1.58, P = 0.031), respectively. Hazard ratios (95% CIs) for all-cause mortality among those with and without CKD were 0.96 (0.70-1.31, P = 0.792) and 1.40 (1.08-1.82, P = 0.011), respectively (P for interaction, 0.071), and those for HF hospitalization among those with and without CKD were 0.99 (0.74-1.33, P = 0.942) and 1.49 (1.19-1.86, P = 0.001), respectively (P for interaction, 0.033). CONCLUSION: Hyperuricaemia has a significant association with poor outcomes in HF patients without CKD but not in those with CKD, suggesting that hyperuricaemia may predict poor outcomes when it is primarily a marker of increased xanthine oxidase activity, but not when it is primarily due to impaired renal excretion of uric acid.

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.

Effects of right ventricular ejection fraction on outcomes in chronic systolic heart failure.

BACKGROUND: Studies of the effect of right ventricular ejection fraction (RVEF) on outcomes in heart failure (HF) are limited by small sample size and short follow-up. METHODS AND RESULTS: We examined the effect of baseline RVEF on outcomes in 2008 Beta-Blocker Evaluation of Survival Trial (BEST) participants with HF and left ventricular ejection fraction or=40% (n=733), 30% to 39% (n=531), 20% to 29% (n=473), and <20% (n=271). Unadjusted rates for all-cause mortality in patients with RVEF >or=40%, 30% to 39%, 20% to 29%, and <20% were 27%, 32%, 35%, and 47%, respectively. When compared with patients with RVEF >or=40%, unadjusted hazard ratios and 95% confidence intervals for all-cause mortality for those with RVEF 30% to 39%, 20% to 29%, and <20% were 1.19 (0.97 to 1.46; P=0.087), 1.45 (1.17 to 1.78; P=0.001), and 1.98 (1.59 to 2.47; P<0.0001), respectively. Respective multivariable-adjusted hazard ratios (95% confidence intervals) for all-cause mortality associated with RVEF 30% to 39%, 20% to 29%, and <20% were 1.07 (0.87 to 1.32; P=0.518), 1.12 (0.89 to 1.40; P=0.328), and 1.32 (1.02 to 1.71; P=0.034), respectively. Adjusted hazard ratios (95% confidence intervals) for other outcomes associated with RVEF <20% (compared with >or=40%) were as follows: cardiovascular mortality, 1.33 (1.01 to 1.76; P=0.041); HF mortality, 1.61 (1.03 to 2.52; P=0.037); sudden cardiac death, 1.29 (0.87 to 1.91; P=0.212); all-cause hospitalization, 1.21 (1.00 to 1.47; P=0.056); and HF hospitalization, 1.39 (1.10 to 1.77; P=0.007). CONCLUSIONS: Baseline RVEF <20% is a significant independent predictor of mortality and HF hospitalization in systolic HF.

Heart failure is a risk factor for incident driving cessation among community-dwelling older adults: findings from a prospective population study.

BACKGROUND: Heart failure (HF) patients often depend on driving for access to specialty care. We analyzed a public-use copy of the Cardiovascular Health Study (CHS) data to determine if HF is a risk factor for driving cessation and to identify other risk factors for driving cessation among those with HF. METHODS AND RESULTS: Of the 5,383 community-dwelling drivers aged ≥65 years (mean age 73 years, 55% women, 13% African American), 839 had HF: 246 had baseline prevalent HF and 593 developed incident HF before driving cessation during 9 years of follow-up. Incident driving cessation occurred at rates of 3,980 and 3,709 per 10,000 person-years of follow-up for those with and without HF, respectively (unadjusted hazard ratio [HR] associated with HF as a time-varying variable: 2.13, 95% confidence interval [CI] 1.83-2.47; P < .001). This association remained unchanged after multivariable risk adjustment (HR 1.43, 95% CI 1.21-1.68; P < .001). Among the 839 older drivers with HF, independent predictors for incident driving cessation were age ≥75 years (HR 1.99, 95% CI 1.44-2.73; P < .001), female gender (HR 1.93, 95% CI 1.37-2.74; P < .001), difficulty walking half a mile (HR 1.47 (1.04-2.08); P = .028), vision problems (HR 1.47, 95% CI 1.07-2.02; P = .018), and stroke as a time-varying covariate (HR 1.96, 95% CI 1.38-2.79; P < .001). CONCLUSIONS: HF is an independent risk factor for incident driving cessation among community-dwelling older drivers. Several patient characteristics predicted driving cessation in older HF patients, which may be targets for interventions to prevent driving cessation among these patients.

Relationship between stage of kidney disease and incident heart failure in older adults.

BACKGROUND: The relationship between stage of chronic kidney disease (CKD) and incident heart failure (HF) remains unclear. METHODS: Of the 5,795 community-dwelling adults ≥65 years in the Cardiovascular Health Study, 5,450 were free of prevalent HF and had baseline estimated glomerular filtration rate (eGFR: ml/min/1.73 m(2)) data. Of these, 898 (16%) had CKD 3A (eGFR 45-59 ml/min/1.73 m(2)) and 242 (4%) had CKD stage ≥3B (eGFR <45 ml/min/1.73 m(2)). Data on baseline proteinuria were not available and 4,310 (79%) individuals with eGFR ≥60 ml/min/1.73 m(2) were considered to have no CKD. Propensity scores estimated separately for CKD 3A and ≥3B were used to assemble two cohorts of 1,714 (857 pairs with CKD 3A and no CKD) and 557 participants (148 CKD ≥3B and 409 no CKD), respectively, balanced on 50 baseline characteristics. RESULTS: During 13 years of follow-up, centrally-adjudicated incident HF occurred in 19, 24 and 38% of pre-match participants without CKD (reference), with CKD 3A [unadjusted hazard ratio (HR) 1.40; 95% confidence interval (CI) 1.20-1.63; p < 0.001] and with CKD ≥3B (HR 3.37; 95% CI 2.71-4.18; p < 0.001), respectively. In contrast, among matched participants, incident HF occurred in 23 and 23% of those with CKD 3A and no CKD, respectively (HR 1.03; 95% CI 0.85-1.26; p = 0.746), and 36 and 28% of those with CKD ≥3B and no CKD, respectively (HR 1.44; 95% CI 1.04-2.00; p = 0.027). CONCLUSIONS: Among community-dwelling older adults, CKD is a marker of incident HF regardless of stage; however, CKD ≥3B, not CKD 3A, has a modest independent association with incident HF.

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.

Assessing changes in relapse rates in multiple sclerosis.

Multiple Sclerosis (MS) annualized relapse rates (ARRs) in trials may be declining due to changes in diagnostic criteria, MS etiology, study criteria, and selection biases. This review examines if there is a trend in the ARR for relapsing-remitting MS patients (RRMS) over time and if so, why. A comprehensive literature search was performed using PubMed, Web of Science(®), and the Cochrane Library using electronic searches, screen scraping for abstracts, and hand searching of references for randomized trials conducted between 1960 and 2008. Out of 72 randomized trials, 56 (77.8%) defined relapse. This study uses 32 placebo relapsing-remitting studies out of the 37 (66.1%) with RRMS. The mean ARR for the treatment arms was 0.68 and the one for the placebo groups was 1.002. The year of publication was negatively associated with the ARR (p = 0.0001). The annual reduction amounts to 0.36 relapses over a 10-year period. Age and duration of symptoms were negatively associated with the ARR. Year of publication was significantly negatively associated with ARR after controlling for covariates. ARRs have fallen with relapse definition, entrance criteria remain important, but time exceeds all these variables and reflects two likely sources, selection of patients for trials by clinicians and rescue of patients truncating the number of multiple relapses. The impact of truncating the number of relapses on the falling rates is important, not only on the ARRs, but also on the impact of informative censoring in drop-outs.

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.

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.

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.