Kavitha Nutakki

Use of diffusion-weighted MRI to differentiate chronic pancreatitis from pancreatic cancer

OBJECTIVE The purpose of this study was to compare diffusion-weighted MRI (DWI) and conventional (non-DWI) MRI sequences in differentiating mass-forming chronic pancreatitis from pancreatic cancer. MATERIALS AND METHODS A retrospective cohort study included 36 patients who underwent pancreatic resection for pancreatic cancer (n = 13) and chronic pancreatitis (n = 23) after preoperative MRI with DWI. Two independent reviewers assessed the DW images for signal intensity and apparent diffusion coefficient (ADC) values. Four weeks later, they reviewed the other MR images for size of mass, double-duct sign, pancreatic duct cutoff, and perivascular soft-tissue cuffing. A score for conventional MRI was given with 1 meaning definitely benign and 5 meaning definitely malignant. Univariate and multivariate analyses and receiver operating characteristic (ROC) curve analysis were performed with surgical pathologic examination as the reference standard. RESULTS The only finding that differentiated the two groups was the presence of a well-defined mass, favoring the diagnosis of cancer (p = 0.02, p < 0.01). There was no significant difference between the two groups in signal intensity on DW images (p = 0.82, p = 0.85) or ADC (p = 0.51, p = 0.76). Double-duct sign, pancreatic duct cutoff, and perivascular soft-tissue cuffing were not useful in differentiating the two groups. The areas under the ROC curve were 0.873 and 0.878 for the conventional MRI scores, compared with 0.602 and 0.552 for ADC measurements (p = 0.02, p = 0.008). CONCLUSION The addition of DWI to conventional MRI does not facilitate differentiation of pancreatic cancer from chronic pancreatitis.

Development of the Adult PedsQL™ Neurofibromatosis Type 1 Module: Initial Feasibility, Reliability and Validity

BackgroundNeurofibromatosis type 1 (NF1) is a common autosomal dominant genetic disorder with significant impact on health-related quality of life (HRQOL). Research in understanding the pathogenetic mechanisms of neurofibroma development has led to the use of new clinical trials for the treatment of NF1. One of the most important outcomes of a trial is improvement in quality of life, however, no condition specific HRQOL instrument for NF1 exists. The objective of this study was to develop an NF1 HRQOL instrument as a module of PedsQL™ and to test for its initial feasibility, internal consistency reliability and validity in adults with NF1.MethodsThe NF1 specific HRQOL instrument was developed using a standard method of PedsQL™ module development – literature review, focus group/semi-structured interviews, cognitive interviews and experts’ review of initial draft, pilot testing and field testing. Field testing involved 134 adults with NF1. Feasibility was measured by the percentage of missing responses, internal consistency reliability was measured with Cronbach’s alpha and validity was measured by the known-groups method.ResultsFeasibility, measured by the percentage of missing responses was 4.8% for all subscales on the adult version of the NF1-specific instrument. Internal consistency reliability for the Total Score (alpha =0.97) and subscale reliabilities ranging from 0.72 to 0.96 were acceptable for group comparisons. The PedsQL™ NF1 module distinguished between NF1 adults with excellent to very good, good, and fair to poor health status.ConclusionsThe results demonstrate the initial feasibility, reliability and validity of the PedsQL™ NF1 module in adult patients. The PedsQL™ NF1 Module can be used to understand the multidimensional nature of NF1 on the HRQOL patients with this disorder.

The health-related quality of life of children, adolescents, and young adults with neurofibromatosis type 1 and their families: Analysis of narratives

PURPOSE Provide an in-depth description of the health-related quality of life (HRQoL) in youth diagnosed with neurofibromatosis type 1 (NF1) and their families. DESIGN AND METHODS Data were drawn from qualitative interviews conducted for a larger study aimed at developing the Pediatric Quality of Life Inventory™ (PedsQL™) NF1 module. RESULTS Youth with NF1 and their families experience a wide range of concerns related to HRQoL due to the varied symptom expression and uncertain trajectory of the disorder. PRACTICE IMPLICATIONS Pediatric nurses should routinely assess for HRQoL in this population and develop strategies tailored to those concerns that require intervention.

The Prevalence of At-Risk Development in Children 30 to 60 Months Old Presenting With Disruptive Behaviors

Objective. This study assessed the prevalence of failed developmental screens in 30- to 60-month-old children who presented with a behavioral complaint of disruptive behavior to a referral clinic. Methods. A retrospective chart review was performed in a specialty behavioral pediatric clinic. Outcome measures were obtained from children referred to the clinic with parental concern of disruptive behavior. Results. Out of 151 patients, 66% (99/151) had been screened for developmental delays with a formal screening instrument. Of these, 71% (70/99) failed developmental screening in one or more domains. Conclusions. Preschoolers referred to a behavioral clinic for parental concerns of disruptive behaviors were more than 4 times more likely to be at risk for developmental delays than the general population, with a majority of suspected delays in communication and problem-solving domains. This finding suggests that developmental screening should be a part of the initial workup for children with disruptive behaviors.

Development of the pediatric quality of life inventory neurofibromatosis type 1 module items for children, adolescents and young adults: qualitative methods

Health-related quality of life (HRQOL) is arguably one of the most important measures in evaluating effectiveness of clinical treatments. At present, there is no disease-specific outcome measure to assess the HRQOL of children, adolescents and young adults with Neurofibromatosis Type 1 (NF1). This study aimed to develop the items and support the content validity for the Pediatric Quality of Life Inventory™ (PedsQL™) NF1 Module for children, adolescents and young adults. The iterative process included multiphase qualitative methods including a literature review, survey of expert opinions, semi-structured interviews, cognitive interviews and pilot testing. Fifteen domains were derived from the qualitative methods, with content saturation achieved, resulting in 115 items. The domains include skin, pain, pain impact, pain management, cognitive functioning, speech, fine motor, balance, vision, perceived physical appearance, communication, worry, treatment, medicines and gastrointestinal symptoms. This study is limited because all participants are recruited from a single-site. Qualitative methods support the content validity for the PedsQL™ NF1 Module for children, adolescents and young adults. The PedsQL™ NF1 Module is now undergoing national multisite field testing for the psychometric validation of the instrument development.

PedsQL Neurofibromatosis Type 1 Module for children, adolescents and young adults: feasibility, reliability, and validity

The objective of the present study was to report on the measurement properties of the Pediatric Quality of Life Inventory (PedsQL) Neurofibromatosis Type 1 Module for pediatric patients ages 5–25 from the perspectives of patients and parents. The 104-item PedsQL NF1 Module and 23-item PedsQL Generic Core Scales were completed in a multi-site national study by 323 patients and 335 parents (343 families). Patients were diagnosed with NF1 using the National Institutes of Health diagnostic criteria. In addition to a Total Scale Score, 18 unidimensional scales were derived measuring skin itch bother, skin sensations, pain, pain impact, pain management, cognitive functioning, speech, fine motor, balance, vision, perceived physical appearance, communication, worry, treatment anxiety, medicines, stomach discomfort, constipation, and diarrhea. The PedsQL NF1 Module Scales evidenced excellent feasibility, excellent reliability for the Total Scale Scores (patient self-report α = 0.98; parent proxy-report α = 0.98), and good to excellent reliability for the 18 individual scales (patient self-report α = 0.71–0.96; parent proxy-report α = 0.73–0.98). Intercorrelations with the Generic Core Scales supported construct validity. Factor analysis supported the unidimensionality of the 18 individual scales. The PedsQL NF1 Module Scales demonstrated acceptable to excellent measurement properties, and may be utilized as standardized metrics to assess NF1-specific symptoms and problems in clinical research and practice in children, adolescents, and young adults.

519 Predictors of Mortality in Individuals With Nonalcoholic Fatty Liver Disease (NAFLD) in the United States: Results From the Third National Health and Nutrition Examination Survey (NHANES III)

Background: Previous cross-sectional studies have shown that serum levels of cytokeratin fragments (CK18) are associated with the presence of steatohepatitis in individuals with nonalcoholic fatty liver disease (NAFLD). However, it is unknown if serial serum CK18 levels can predict longitudinal changes in liver histology in NAFLD. Aim: To determine the degree to which changes in serum CK18 associate with changes in liver histology over a 96-week period in adult patients with nonalcoholic steatohepatitis (NASH). Methods: Serum CK18 levels were measured at baseline and 16, 48, and 96 weeks in 231 of the 247 adults with NASH who participated in the PIVENS trial which investigated the efficacy of pioglitazone vs. vitamin E vs. placebo in non-diabetic individuals with histologically confirmed NASH over a 96-week period. Liver biopsies at baseline and after 96 weeks of treatment were centrally evaluated by the NASH CRN Pathology Committee. Multiple logistic (for categorical outcomes) and linear (for continuous outcome variables) regression models were used to determine the association between changes in histological features, ALT, and % collagen assessed by Sirius red staining, and change in CK18 levels, controlling for baseline CK18 levels and treatment group. Results: At baseline, CK18 levels among the 3 treatment groups were similar (placebo: 440± 350 U/L, vit E: 510± 350 U/L, and pioglitazone: 490± 410 U/L). Compared to placebo, serum CK18 levels among individuals treated with vit E were reduced at week 16 (mean change from baseline -160± 300 vs. -50 ±380 U/L, p= 0.02), week 48 (-220± 390 vs. -10± 370 U/L, p=0.009), and week 96 (-200± 400 vs. 30± 400 U/L, p=0.009). Similarly, compared to placebo, serum CK18 levels among individuals treated with pioglitazone were reduced at week 16 (mean change from baseline -240 ± 390 vs. -50± 380 U/L, p,=0.001), week 48 (-180± 370 vs. -10± 370 U/L, p=0.001, and week 96 (-260 ±400 vs. 30 ± 400 U/L, p=0.001). Strong correlations were seen with change in CK18 levels and the primary histologic endpoint, resolution of NASH, and individual histologic features of NASH (Table 1). In addition, change in CK18 levels strongly correlated with change in ALT levels (b=0.06, 95% CI: 0.04, 0.08; P,0.001).Percent collagen measurements were not related to change in CK18 (b=-0.17 %/100*U/L , 95% CI:-0.70, 0.37; P= 0.54). Summary: (1) Compared to placebo, treatment with vit E or pioglitazone had significant reduction in serum CK18 levels. (2) Changes in serum CK18 correlated with histologic improvement in non-diabetic adults with NASH treated with vitamin E or pioglitazone. Conclusion: Serum CK18 is a potential useful surrogate marker for detection of improvement in clinical trials.