Desmoplakin Cardiomyopathy, a Fibrotic and Inflammatory Form of Cardiomyopathy Distinct From Typical Dilated or Arrhythmogenic Right Ventricular Cardiomyopathy.

BACKGROUND: Mutations in desmoplakin (DSP), the primary force transducer between cardiac desmosomes and intermediate filaments, cause an arrhythmogenic form of cardiomyopathy that has been variably associated with arrhythmogenic right ventricular cardiomyopathy. Clinical correlates of DSP cardiomyopathy have been limited to small case series. METHODS: Clinical and genetic data were collected on 107 patients with pathogenic DSP mutations and 81 patients with pathogenic plakophilin 2 (PKP2) mutations as a comparison cohort. A composite outcome of severe ventricular arrhythmia was assessed. RESULTS: DSP and PKP2 cohorts included similar proportions of probands (41% versus 42%) and patients with truncating mutations (98% versus 100%). Left ventricular (LV) predominant cardiomyopathy was exclusively present among patients with DSP (55% versus 0% for PKP2, P<0.001), whereas right ventricular cardiomyopathy was present in only 14% of patients with DSP versus 40% for PKP2 (P<0.001). Arrhythmogenic right ventricular cardiomyopathy diagnostic criteria had poor sensitivity for DSP cardiomyopathy. LV late gadolinium enhancement was present in a primarily subepicardial distribution in 40% of patients with DSP (23/57 with magnetic resonance images). LV late gadolinium enhancement occurred with normal LV systolic function in 35% (8/23) of patients with DSP. Episodes of acute myocardial injury (chest pain with troponin elevation and normal coronary angiography) occurred in 15% of patients with DSP and were strongly associated with LV late gadolinium enhancement (90%), even in cases of acute myocardial injury with normal ventricular function (4/5, 80% with late gadolinium enhancement). In 4 DSP cases with 18F-fluorodeoxyglucose positron emission tomography scans, acute LV myocardial injury was associated with myocardial inflammation misdiagnosed initially as cardiac sarcoidosis or myocarditis. Left ventricle ejection fraction <55% was strongly associated with severe ventricular arrhythmias for DSP cases (P<0.001, sensitivity 85%, specificity 53%). Right ventricular ejection fraction <45% was associated with severe arrhythmias for PKP2 cases (P<0.001) but was poorly associated for DSP cases (P=0.8). Frequent premature ventricular contractions were common among patients with severe arrhythmias for both DSP (80%) and PKP2 (91%) groups (P=non-significant). CONCLUSIONS: DSP cardiomyopathy is a distinct form of arrhythmogenic cardiomyopathy characterized by episodic myocardial injury, left ventricular fibrosis that precedes systolic dysfunction, and a high incidence of ventricular arrhythmias. A genotype-specific approach for diagnosis and risk stratification should be used.

Speech difficulties and patient health communication mediating effects on worry and health-related quality of life in children, adolescents, and young adults with Neurofibromatosis Type 1.

The objective was to investigate the serial mediating effects of speech difficulties, patient health communication, and disease-specific worry in the relationship between neurofibromatosis (NF) symptoms (pain and skin symptoms) and total generic health-related quality of life (HRQOL) in children, adolescents, and young adults with NF Type 1 (NF1) from the patient perspective. The Speech, Communication, Worry, Pain, Skin Itch Bother, and Skin Sensations Scales from the Pediatric Quality of Life Inventory (PedsQL) NF1 Module and the PedsQL 4.0 Generic Core Scales were completed in a multi-site national study by 305 patients ages 5-25 years. A serial multiple mediator model analysis was conducted to test the hypothesized sequential mediating effects of speech difficulties, health communication, and worry as intervening variables in the association between NF1 symptoms and HRQOL. Symptoms predictive effects on total generic HRQOL were serially mediated by speech difficulties, patient health communication, and worry. In predictive analytics models utilizing hierarchical multiple regression analyses with age and gender demographic covariates, the pain, skin itch bother, and skin sensations multiple mediator models accounted for 61%, 59%, and 56% of the variance in generic HRQOL (p < .001), reflecting large effect sizes. Speech difficulties, patient health communication, and disease-specific worry explain in part the mechanism of symptoms predictive effects on total generic HRQOL in pediatric patients with NF1. Identifying NF1-specific predictors and serial mediators of total generic HRQOL in pediatric patients with NF1 from the patient perspective enables a patient-centered comprehensive care approach for children, adolescents, and young adults with NF1.

Pain, skin sensations symptoms, and cognitive functioning predictors of health-related quality of life in pediatric patients with Neurofibromatosis Type 1.

OBJECTIVES: The aim was to investigate pain, skin sensations symptoms and patient self-reported, and parent proxy-reported cognitive functioning as predictors of generic health-related quality of life (HRQOL) in pediatric patients with Neurofibromatosis Type 1 (NF1) from the perspectives of patients and parents. METHODS: The Pain, Skin Itch Bother, Skin Sensations, and Cognitive Functioning Scales from the PedsQL™ Neurofibromatosis Type 1 Module and the PedsQL™ Generic Core Scales were completed in a multi-site national study by 323 patients and 335 parents. Patients were 5-25 years of age. Pain and skin symptoms and cognitive functioning were tested for bivariate and multivariate linear associations with generic HRQOL. RESULTS: Pain, skin itch bother, skin sensations, and cognitive functioning were associated with decreased HRQOL in bivariate analyses (Ps < 0.001). In predictive analytics models, utilizing hierarchical multiple regression analyses controlling for demographic covariates, pain, skin itch bother, skin sensations, and cognitive functioning as a group accounted for 61 percent of the variance in patient-reported generic HRQOL (P < 0.001), reflecting a large effect size. For parent proxy-report, the predictor variables as a group accounted for 53% of the variance in generic HRQOL. CONCLUSIONS: Pain, skin symptoms, and patient self-reported and parent proxy-reported cognitive functioning are key predictors of generic HRQOL in pediatric patients with NF1. Delineating NF1-specific symptoms and cognitive functioning as high-priority predictors from the patient and parents perspective enhances a family-centered approach in clinical research, clinical trials, and clinical practice intended to improve the global generic HRQOL of pediatric patients with NF1.

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.

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.

Effectiveness of cross-cultural education for medical residents caring for burmese refugees.

BACKGROUND: Limited resources are available to educate health professionals on cultural considerations and specific healthcare needs of Burmese refugees. The objective of this study was to determine the effectiveness of a module focused on cross-cultural considerations when caring for Burmese refugees. METHODS: A brief educational module using anonymously tracked pre- and post-intervention, self-administered surveys was developed and studied. The surveys measured pediatric and family medicine residents' knowledge, attitudes, and comfort in caring for Burmese refugees. Paired t-tests for continuous variables and Fisher's exact tests for categorical variables were used to test pre- and post-intervention differences. We included open-ended questions for residents to describe their experiences with the Burmese population. RESULTS: The survey was available to 173 residents. Forty-four pre- and post-intervention surveys were completed (response rate of 25%). Resident comfort in caring for Burmese increased significantly after the module (P = 0.04). Resident knowledge of population-specific cultural information increased regarding ethnic groups (P = 0.004), appropriate laboratory use (P = 0.04), and history gathering (P = 0.001). Areas of improved resident attitudes included comprehension of information from families (P = 0.03) and length of time required with interpreter (P = 0.01). Thematic evaluation of qualitative data highlighted four themes: access to interpreter and resources, verbal communication, nonverbal communication, and relationship building with cultural considerations. DISCUSSION: A brief intervention for residents has the potential to improve knowledge, attitudes, and comfort in caring for Burmese patients. Interventions focused on cultural considerations in medical care may improve cultural competency when caring for vulnerable patient populations.

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.

Usefulness of conventional MRI sequences and diffusion-weighted imaging in differentiating malignant from benign portal vein thrombus in cirrhotic patients.

OBJECTIVE: The objective of our study was to determine the value of diffusion-weighted imaging (DWI) and conventional MRI (non-DWI sequences) in differentiating benign portal vein thrombus (PVT) from malignant PVT in cirrhotic patients. MATERIALS AND METHODS: A retrospective search of the department of radiology's MRI database of examinations performed from October 2006 through December 2010 for "portal vein thrombosis" and "cirrhosis" and "hepatocellular cancer" was performed. Patients who underwent diagnostic DWI and had thrombus shown to be rapidly (< 3 months) increasing in size despite anticoagulation therapy were considered to have malignant PVT (n = 16 cases) and patients with MRI findings showing stability or reduction in the extent of thrombus over a 12-month follow-up were considered to have benign PVT (n = 20 cases). Two blinded and independent reviewers analyzed the DW images and conventional MR images. RESULTS: There was no difference in the distribution of patients by age (p = 0.25) or sex (p = 0.68) between the benign and malignant PVT groups. On multivariate analysis, the only parameter to predict the type of PVT was the size of HCC (p = 0.05); other parameters were excluded from the model. There was substantial overlap in apparent diffusion coefficient (ADC) values and PVT/liver ADC ratios of benign PVT and malignant PVT. The presence of at least two of the three following MRI findings had a sensitivity of 100% and specificity of 90% for the diagnosis of malignant PVT: distance from tumor to PVT of less than 2 cm, HCC size of greater than 5 cm, and arterial enhancement of PVT. CONCLUSION: Signal-intensity characteristics on DWI and measured ADC values do not reliably differentiate benign PVT from malignant PVT. On the other hand, careful assessment of conventional MRI findings may allow this distinction, thus obviating biopsy.

Development of the adult PedsQL™ neurofibromatosis type 1 module: initial feasibility, reliability and validity.

BACKGROUND: Neurofibromatosis 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. METHODS: The 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. RESULTS: Feasibility, 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. CONCLUSIONS: The 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.

Cognitive functioning and pain interference mediate pain predictive effects on health-related quality of life in pediatric patients with Neurofibromatosis Type 1.

OBJECTIVES: The objective was to investigate the serial mediating effects of perceived cognitive functioning and pain interference in daily living in the relationship between perceived pain and overall generic health-related quality of life (HRQOL) in children, adolescents, and young adults with Neurofibromatosis Type 1 (NF1). METHODS: The Pain, Cognitive Functioning, and Pain Impact Scales from the PedsQL Neurofibromatosis Type 1 Module and the PedsQL 4.0 Generic Core Scales were completed in a multi-site national study by 323 patients ages 5-25 and 335 parents. A serial multiple mediator model analysis was conducted to test the hypothesized sequential mediating effects of cognitive functioning and pain interference as intervening variables in the association between pain as a predictor variable and overall generic HRQOL. RESULTS: Pain predictive effects on overall generic HRQOL were serially mediated by cognitive functioning and pain interference. In predictive analytics models utilizing hierarchical multiple regression analyses with age and gender demographic covariates, pain, cognitive functioning and pain interference accounted for 66% of the variance in patient-reported generic HRQOL and 57% of the variance in parent proxy-reported generic HRQOL (P < 0.001), reflecting large effect sizes. CONCLUSIONS: Cognitive functioning and pain interference explain in part the mechanism of pain predictive effects on overall generic HRQOL in pediatric patients with NF1. Identifying NF1-specific pain, cognitive functioning, and pain interference as salient predictors of overall generic HRQOL from the patient and parent perspective facilitates a family-centered orientation to the comprehensive care of children, adolescents, and young adults with NF1.

New-onset arrhythmia associated with patients hospitalized for thyroid dysfunction.

BACKGROUND: Thyroid dysfunction has been associated with cardiovascular dysfunction in the literature. However, the frequency of new-onset arrhythmias associated with thyroid disease hospitalization is unknown. Hence, we analyzed frequency, in-hospital outcomes, and resource utilization of new-onset arrhythmias associated with thyroid dysfunction hospitalizations. METHODS: The patients who were admitted with the primary reason of thyroid dysfunction were included using appropriate international classification of disease, ninth revision, clinical modification (ICD-9-CM) codes. We then identified new-onset arrhythmias using appropriate ICD-9-CM codes. We utilized the "present on admission" variable to exclude arrhythmias that were present on admission. RESULTS: Among the eligible patients with thyroid dysfunction, only 3% (n=12,111) developed a new-onset arrhythmia. Atrioventricular block (1.49%) is the most frequent followed by atrial fibrillation (0.92%), ventricular tachycardia (0.47%), atrial flutter (0.23%), supraventricular tachycardia (0.1%) and ventricular fibrillation (0.07%). Patients with new-onset arrhythmias were older (mean age 76.7±12.5 years), more predominantly white (n=9008, 74.4%), higher females (n= 7632, 63%), and had a higher frequency of comorbidities. In-hospital mortality occurred in 827 (6.8%) patients with new-onset arrhythmias and 8632 (2.2%) patients without new-onset arrhythmias (P-value <0.001). The medical length of stay and cost of hospitalization was also higher in these patients. CONCLUSION: Thyroid dysfunction is not associated with significantly higher rates of new-onset arrhythmias while inpatient. However, when developed, these arrhythmias are associated with higher mortality and resource utilization. The patients admitted to the hospital should have thyroid function checked when found to have an arrhythmia.

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.

Database queries for hospitalizations for acute congestive heart failure: flexible methods and validation based on set theory.

BACKGROUND AND OBJECTIVE: Electronic health records databases are increasingly used for identifying cohort populations, covariates, or outcomes, but discerning such clinical 'phenotypes' accurately is an ongoing challenge. We developed a flexible method using overlapping (Venn diagram) queries. Here we describe this approach to find patients hospitalized with acute congestive heart failure (CHF), a sampling strategy for one-by-one 'gold standard' chart review, and calculation of positive predictive value (PPV) and sensitivities, with SEs, across different definitions. MATERIALS AND METHODS: We used retrospective queries of hospitalizations (2002-2011) in the Indiana Network for Patient Care with any CHF ICD-9 diagnoses, a primary diagnosis, an echocardiogram performed, a B-natriuretic peptide (BNP) drawn, or BNP >500 pg/mL. We used a hybrid between proportional sampling by Venn zone and over-sampling non-overlapping zones. The acute CHF (presence/absence) outcome was based on expert chart review using a priori criteria. RESULTS: Among 79,091 hospitalizations, we reviewed 908. A query for any ICD-9 code for CHF had PPV 42.8% (SE 1.5%) for acute CHF and sensitivity 94.3% (1.3%). Primary diagnosis of 428 and BNP >500 pg/mL had PPV 90.4% (SE 2.4%) and sensitivity 28.8% (1.1%). PPV was <10% when there was no echocardiogram, no BNP, and no primary diagnosis. 'False positive' hospitalizations were for other heart disease, lung disease, or other reasons. CONCLUSIONS: This novel method successfully allowed flexible application and validation of queries for patients hospitalized with acute CHF.

Implementation of 24/7 radiology services in an academic medical centre level 1 trauma centre: impact on trauma resuscitation unit length of stay and economic benefit analysis.

STUDY OBJECTIVE: To evaluate the impact of 24/7 radiology services on trauma resuscitation unit (TRU) length of stay (LOS) for patients with minor trauma and to analyse the economic benefits of such an impact from trauma centre perspective. METHODS: The study was HIPAA compliant and had IRB approval. Data were extracted from hospital and radiology information systems. Inclusion criteria specified patients: (a) with minor trauma (i.e., Injury Severity Score<16 and Maximum Abbreviated Injury Scale<4); (b) cross-sectional imaging performed between 12 and 7AM; and (c) admission during 2006 (before 24/7 coverage; comparison group 1) or 2007 (24/7 coverage). Mean, median, standard deviation, and variance for the groups were determined. The theoretical economic benefit achieved with 24/7 radiology coverage was estimated from decreases in TRU LOS for each patient. RESULTS: Totals of 1087 and 1323 patients for 2006 and 2007, respectively, met our selection criteria. Mean TRU LOS decreased from 11.19 to 8.25 h (26%; P<0.001). The median decreased from 10.8 to 7.2 h (33%; P<0.001). The (Q3-Q1) indicator, used as a proxy for variance and spread, decreased from 7.36 to 5.76 h. Theoretical economic benefits from 24/7 radiology coverage were achieved by the product of TRU bed fixed costs with mean decrease in TRU LOS for the calendar year 2007, which equaled $340,069. CONCLUSION: The economic benefits of 24/7 radiology services are related to LOS, which can be shortened by limiting patient discharge delays resulting from report unavailability. This can be a cost-saving replacement for conventional radiology practice when the trauma centre makes appropriate use of vacant TRU beds to realise its opportunity cost.

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.