Abstract Objective National consensus statements recommend that providers regularly assess the transition readiness skills of adolescent and young adults (AYA). In 2010 we developed a 29-item version ...of Transition Readiness Assessment Questionnaire (TRAQ). We reevaluated item performance and factor structure, and reassessed the TRAQ's reliability and validity. Methods We surveyed youth from 3 academic clinics in Jacksonville, Florida; Chapel Hill, North Carolina; and Boston, Massachusetts. Participants were AYA with special health care needs aged 14 to 21 years. From a convenience sample of 306 patients, we conducted item reduction strategies and exploratory factor analysis (EFA). On a second convenience sample of 221 patients, we conducted confirmatory factor analysis (CFA). Internal reliability was assessed by Cronbach's alpha and criterion validity. Analyses were conducted by the Wilcoxon rank sum test and mixed linear models. Results The item reduction and EFA resulted in a 20-item scale with 5 identified subscales. The CFA conducted on a second sample provided a good fit to the data. The overall scale has high reliability overall (Cronbach's alpha = .94) and good reliability for 4 of the 5 subscales (Cronbach's alpha ranging from .90 to .77 in the pooled sample). Each of the 5 subscale scores were significantly higher for adolescents aged 18 years and older versus those younger than 18 ( P < .0001) in both univariate and multivariate analyses. Conclusions The 20-item, 5-factor structure for the TRAQ is supported by EFA and CFA on independent samples and has good internal reliability and criterion validity. Additional work is needed to expand or revise the TRAQ subscales and test their predictive validity.
To describe the frequency and severity of ototoxicity in a series of pediatric patients treated with platinum-based chemotherapy.
Serial audiologic evaluations were conducted for 67 patients aged 8 ...months to 23 years who received platinum-based chemotherapy. Audiologic data was analyzed to determine time to hearing-loss using American Speech-Language-Hearing Association (ASHA) criteria, and the effects of treatment and patient characteristics on the incidence and severity of ototoxicity.
Bilateral decreases in hearing were seen in 61% of patients (median time to hearing loss, 135 days). Children treated for medulloblastoma, osteosarcoma, and neuroblastoma had greater incidence and severity of hearing loss. Agreement between the usually reported National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) and ASHA criteria was inadequate.
Traditional reporting of toxicity data (CTCAE) has under-reported ototoxicity and minimized the significance of hearing loss in children. As pediatric patients experience improved survival, the effects and implications of high-frequency hearing loss with regard to academic achievement and speech and language development are important considerations, especially in patients younger than 5 years.
OBJECTIVE:To describe and correlate neurotoxicity indicators in long-term primary CNS lymphoma (PCNSL) survivors who were treated with high-dose methotrexate–based regimens with or without ...whole-brain radiotherapy (WBRT).
METHODS:Eighty PCNSL survivors from 4 treatment groups (1 with WBRT and 3 without WBRT) who were a minimum of 2 years after diagnosis and in complete remission underwent prospective neuropsychological, quality-of-life (QOL), and brain MRI evaluation. Clinical characteristics were compared among treatments by using the χ test and analysis of variance. The association among neuroimaging, neuropsychological, and QOL outcomes was assessed by using the Pearson correlation coefficient.
RESULTS:The median interval from diagnosis to evaluation was 5.5 years (minimum, 2 years; maximum, 26 years). Survivors treated with WBRT had lower mean scores in attention/executive function (p = 0.0011), motor skills (p = 0.0023), and neuropsychological composite score (p = 0.0051) compared with those treated without WBRT. Verbal memory was better in survivors with longer intervals from diagnosis to evaluation (p = 0.0045). On brain imaging, mean areas of total T2 abnormalities were different among treatments (p = 0.0006). Total T2 abnormalities after WBRT were more than twice the mean of any non-WBRT group and were associated with poorer neuropsychological and QOL outcomes.
CONCLUSIONS:Our results suggest that in patients treated for PCNSL achieving complete remission and surviving at least 2 years, the addition of WBRT to methotrexate-based chemotherapy increases the risk of treatment-related neurotoxicity. Verbal memory may improve over time.
CLASSIFICATION OF EVIDENCE:This study provides Class III evidence that in patients treated for PCNSL achieving complete remission and surviving at least 2 years, the addition of WBRT to methotrexate-based chemotherapy increases the risk of treatment-related neurotoxicity.
The objective is to describe progressive changes in hearing and cochlear function in children and adolescents treated with platinum-based chemotherapy and to begin preliminary evaluation of the ...feasibility of extended high-frequency audiometry and distortion product otoacoustic emissions for ototoxicity monitoring in children.
Baseline and serial measurement of conventional pure-tone audiometry (0.5 to 8 kHz) and evoked distortion product otoacoustic emissions (DPOAEs) were conducted for 32 patients age 8 months to 20 years who were treated with cisplatin and/or carboplatin chemotherapy. Seventeen children also had baseline and serial measurement of extended high-frequency (EHF) audiometry (9 to 16 kHz). Audiologic data were analyzed to determine the incidence of ototoxicity using the American Speech-Language-Hearing Association criteria, and the relationships between the different measures of ototoxicity.
Of the 32 children, 20 (62.5%) acquired bilateral ototoxicity in the conventional frequency range during chemotherapy treatment, and 26 (81.3%) had bilateral decreases in DPOAE amplitudes and dynamic range. Of the 17 children with EHF audiometry results, 16 (94.1%) had bilateral ototoxicity in the EHF range. Pilot data suggest that EHF thresholds and DPOAEs show ototoxic changes before hearing loss is detected by conventional audiometry.
EHF audiometry and DPOAEs have the potential to reveal earlier changes in auditory function than conventional frequency audiometry during platinum chemotherapy in children.
Sports-related concussion among professional, collegiate, and, more recently, high school athletes has received much attention from the media and medical community. To our knowledge, there is a ...paucity of research regarding parental knowledge of sports-related concussion. The aim of this study was to evaluate parental knowledge of concussion in young children who participated in recreational tackle football.
Parents of children aged 5 years to 15 years attending recreational tackle football games were asked to complete an anonymous questionnaire based on the Centers for Disease Control and Prevention's Heads Up: Concussion in Youth Sports Quiz. The parents were asked about their level of agreement regarding statements that represent definition, symptoms, and treatment of concussion.
A total of 310 of 369 parents (84% response rate) voluntarily completed the questionnaire, with 94% believing that their child had never had a concussion. However, only 13% (n = 41) could correctly identify all seven statements. Most did not identify that a concussion is considered a mild traumatic brain injury and can be achieved from something other than a direct blow to the head. Race, sex, and zip code had no significant association with correctly answering statements. Education (r = 0.24, p < 0.0001) and number of years the child played (r = 0.11, p = 0.049) had a small association. Fifty-three percent and 58% of the parents reported that someone had discussed the definition and the symptoms of concussion with them, respectively, with only about half reporting that information came from their health care provider. No parent was able to classify all symptoms listed as correctly related or not related to concussion. However, identification of correct concussion statements correlated with identification of correct symptoms (r = 0.25, p < 0.001).
While most parents of young athletes demonstrated some knowledge regarding concussion, important misconceptions remain regarding the definition, symptoms, and treatment of concussion. This study highlights the need for health care providers to increase concussion educational efforts.
To evaluate the observed incidence of acute kidney injury (AKI) in adult patients receiving either piperacillin-tazobactam and vancomycin or cefepime-vancomycin for more than 48 hours.
Retrospective ...matched cohort.
Large academic medical center.
Adult patients without preexisting renal dysfunction admitted over an 8-month time period who received either the combination of piperacillin-tazobactam and vancomycin or cefepime-vancomycin for more than 48 hours were evaluated for AKI, defined by the Acute Kidney Injury Network criteria.
A total of 224 patients receiving either antimicrobial combination were evaluated for AKI. The incidence of AKI was significantly higher in the piperacillin-tazobactam and vancomycin group (34.8%) compared with the cefepime-vancomycin group (12.5%) in the unmatched analysis (p<0.0001). After adjusting for potential sources of bias through propensity score matched pairs and conditional logistic regression, piperacillin-tazobactam and vancomycin combination therapy (p=0.003) was an independent predictor of AKI. There were no significant differences in time to AKI or hospital length of stay between groups.
The results of this study suggest that there may be an association between piperacillin-tazobactam and vancomycin combination therapy and increased incidence of AKI.
PURPOSE Primary CNS lymphoma (PCNSL) is confined to the CNS and/or the eyes at presentation and is usually initially treated with intravenous methotrexate-based chemotherapy and whole-brain ...radiotherapy (WBRT). However, the intact blood-brain barrier (BBB) can limit diffusion of methotrexate into brain and tumor. With BBB disruption (BBBD), enhanced drug delivery to the tumor can be achieved. PATIENTS AND METHODS This report summarizes the multi-institutional experience of 149 newly diagnosed (with no prior WBRT) patients with PCNSL treated with osmotic BBBD and intra-arterial (IA) methotrexate at four institutions from 1982 to 2005. In this series, 47.6% of patients were age > or = 60 years, and 42.3% had Karnofsky performance score (KPS) less than 70 at diagnosis. Results The overall response rate was 81.9% (57.8% complete; 24.2% partial). Median overall survival (OS) was 3.1 years (25% estimated survival at 8.5 years). Median progression-free survival (PFS) was 1.8 years, with 5-year PFS of 31% and 7-year PFS of 25%. In low-risk patients (age < 60 years and KPS > or = 70), median OS was approximately 14 years, with a plateau after approximately 8 years. Procedures were generally well tolerated; focal seizures (9.2%) were the most frequent side effect and lacked long-term sequelae. CONCLUSION This large series of patients treated over a 23-year period demonstrates that BBBD/IA methotrexate-based chemotherapy results in successful and durable tumor control and outcomes that are comparable or superior to other PCNSL treatment regimens.
Abstract Purpose Sepsis can lead to poor outcomes when treatment is delayed or inadequate. The purpose of this study was to evaluate outcomes after initiation of a hospital-wide sepsis alert program. ...Materials and methods Retrospective review of patients ≥ 18 years treated for sepsis. Results There were 3917 sepsis admissions: 1929 admissions before, and 1988 in the after phase. Mean age (57.3 vs. 57.1, p = 0.94) and Charlson Comorbidity Scores (2.52 vs. 2.47, p = 0.35) were similar between groups. Multivariable analyses identified significant reductions in the after phase for odds of death (OR 0.62, 95% CI 0.39–0.99, p = 0.046), mean intensive care unit LOS (2.12 days before, 95%CI 1.97, 2.34; 1.95 days after, 95%CI 1.75, 2.06; p < 0.001), mean overall hospital LOS (11.7 days before, 95% CI 10.9, 12.7 days; 9.9 days after, 95% CI 9.3, 10.6 days, p < 0.001), odds of mechanical ventilation use (OR 0.62, 95% CI 0.39, 0.99, p = 0.007), and total charges with a savings of $7159 per sepsis admission ( p = 0.036). There was no reduction in vasopressor use (OR 0.89, 95% CI 0.75, 0.1.06, p = 0.18). Conclusion A hospital-wide program utilizing electronic recognition and RRT intervention resulted in improved outcomes in patients with sepsis.
To compare gadoteridol and ferumoxytol for measurement of relative cerebral blood volume (rCBV) in patients with glioblastoma multiforme (GBM) who showed progressive disease at conventional magnetic ...resonance (MR) imaging after chemo- and radiation therapy (hereafter, chemoradiotherapy) and to correlate rCBV with survival.
Informed consent was obtained from all participants before enrollment in one of four institutional review board-approved protocols. Contrast agent leakage maps and rCBV were derived from perfusion MR imaging with gadoteridol and ferumoxytol in 19 patients with apparently progressive GBM on conventional MR images after chemoradiotherapy. Patients were classified as having high rCBV (>1.75), indicating tumor, and low rCBV (≤ 1.75), indicating pseudoprogression, for each contrast agent separately, and with or without contrast agent leakage correction for imaging with gadoteridol. Statistical analysis was performed by using Kaplan-Meier survival plots with the log-rank test and Cox proportional hazards models.
With ferumoxytol, rCBV was low in nine (47%) patients, with median overall survival (mOS) of 591 days, and high rCBV in 10 (53%) patients, with mOS of 163 days. A hazard ratio of 0.098 (P = .004) indicated significantly improved survival. With gadoteridol, rCBV was low in 14 (74%) patients, with mOS of 474 days, and high in five (26%), with mOS of 156 days and a nonsignificant hazard ratio of 0.339 (P = .093). Five patients with mismatched high rCBV with ferumoxytol and low rCBV with gadoteridol had an mOS of 171 days. When leakage correction was applied, rCBV with gadoteridol was significantly associated with survival (hazard ratio, 0.12; P = .003).
Ferumoxytol as a blood pool agent facilitates differentiation between tumor progression and pseudoprogression, appears to be a good prognostic biomarker, and unlike gadoteridol, does not require contrast agent leakage correction.
Specific drug therapy to target the underlying proinflammatory and prothrombotic state in patients with metabolic syndrome (MS) is lacking. We sought to study the effect of high-intensity ...atorvastatin on markers of lipogenesis, inflammation and thrombogenesis, in women with MS in the absence of cardiovascular disease or diabetes.
This randomized double-blinded controlled trial included 88 women with MS (according to National Cholesterol Education Panel Adult Treatment Panel III criteria) and low atherosclerotic cardiovascular risk. Participants were randomized to receive atorvastatin 80 mg or matching placebo. Thrombogenic, lipogenic and inflammatory markers were collected at the time of enrollment, after a 6-week dietary run-in phase (time of randomization), and at 6- and 12-weeks after randomization. At 6 weeks post-randomization, there was significant reduction in total cholesterol, low density lipoprotein cholesterol, triglycerides, apolipoprotein-B (Apo-B) and Apo-B/Apo-A1 ratio in the atorvastatin arm compared to placebo. This difference persisted at 12-weeks post randomization. There was no significant difference in fasting blood glucose, high-density lipoprotein cholesterol, high sensitivity C-reactive protein, serum leptin, Apo-A1, intercellular adhesion molecule 1 and platelet activity. A significant increase in vascular adhesion molecule 1 at 6 and 12 weeks was seen within the atorvastatin arm. No difference was observed in blood pressure and waist circumference.
In conclusion, high-intensity atorvastatin has an early and significant impact on lipoproteins and apolipoproteins but did not lower inflammatory, thrombogenic or biomarkers of platelet activity and aggregation in women with MS. The use of statins for primary prevention in these patients should be further explored.
•Therapies targeting pro-inflammatory/thrombotic state in metabolic syndrome (MS) are lacking.•We randomized women with MS to high-intensity atorvastatin or placebo and assessed biomarkers.•Total cholesterol, LDL, triglycerides, Apo-B and Apo-B/Apo-A1 decreased in the atorvastatin arm.•Blood glucose, HDL, hs-CRP, leptin, Apo-A1, ICAM-1 and platelet activity remained unchanged.•The use of statins for primary prevention in MS patients should be further explored.
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