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Objective: JDM is associated with multiple potential risk factors for cardiovascular disease, including reduced heart rate variability, systolic/diastolic cardiac dysfunction, abnormal brachial artery reactivity and metabolic syndrome. However, little is known about cardiovascular risk in JDM. We sought to examine the association between JDM and cardiovascular risk factors and disease in US children., Methods: Data from the 2002-12 National Inpatient Sample was analysed, including ∼20% of all US hospitalizations (n = 14 535 620 paediatric hospitalizations)., Results: JDM was significantly associated with 12 of 13 comorbidities, including hypertension [survey logistic regression; crude odds ratio (95% CI): 22.25 (15.51, 31.92)], obesity [5.87 (3.44, 10.02)], uncomplicated diabetes [7.95 (4.21, 15.00)], lipid abnormalities [5.84 (2.77, 12.31)], particularly lipodystrophy [151.08 (38.24, 596.86)], peripheral and visceral atherosclerosis [10.09 (3.70, 27.56)], late effects of cerebrovascular disease [15.49 (2.37, 101.43)], personal history of transient ischaemic attack and cerebral infarction [10.82 (2.46, 47.65)], pulmonary circulatory disorder [12.23 (2.59, 57.73)], arrhythmia [3.93 (2.80, 5.52)], bradycardia [4.22 (2.65, 6.74)] and hypotension [2.62 (1.27, 5.39)]., Conclusions: There are significantly higher odds of cardiovascular and cerebrovascular comorbidities among inpatients with JDM, with adolescents, girls and racial/ethnic minorities being at highest risk.

Objective: To determine the prevalence and risk factors for hospitalization with dermatomyositis and assess inpatient burden of dermatomyositis., Methods: Data on 72,651,487 hospitalizations from the 2002-2012 Nationwide Inpatient Sample, a 20% stratified sample of all acute-care hospitalizations in the US, were analyzed. International Classification of Diseases, Ninth Revision, Clinical Modification coding was used to identify hospitalizations with a diagnosis of dermatomyositis., Results: There were 9,687 and 43,188 weighted admissions with a primary or secondary diagnosis of dermatomyositis, respectively. In multivariable logistic regression models with stepwise selection, female sex (logistic regression: adjusted odds ratio 2.05 [95% confidence interval (95% CI) 1.80, 2.34]), nonwhite race (African American: 1.68 [1.57, 1.79]; Hispanic: 2.38 [2.22, 2.55]; Asian: 1.54 [1.32, 1.81]; and multiracial/other: 1.65 [1.45, 1.88]), and multiple chronic conditions (2-5: 2.39 [2.20, 2.60] and ≥6: 2.80 [2.56, 3.07]) were all associated with higher rates of hospitalization for dermatomyositis. The weighted total length of stay (LOS) and inflation-adjusted cost of care for patients with a primary inpatient diagnosis of dermatomyositis was 80,686 days and $168,076,970, with geometric means of 5.38 (95% CI 5.08, 5.71) and $11,682 (95% CI $11,013, $12,392), respectively. LOS and costs of hospitalization were significantly higher in patients with dermatomyositis compared to those without. Notably, race/ethnicity was associated with increased LOS (log-linear regression: adjusted β [95% CI] for African American: 0.14 [0.04, 0.25] and Asian: 0.38 [0.22, 0.55]) and cost of care (Asian: 0.51 [0.36, 0.67])., Conclusion: There is a significant and increasing inpatient burden for dermatomyositis in the US. There appear to be racial differences, as nonwhites have higher prevalence of admission, increased LOS, and cost of care., (© 2017, American College of Rheumatology.)

Objective: Localized scleroderma can negatively affect children's quality of life (QoL), but predictors of impact have not been well described. We sought to identify predictors of QoL impact in juvenile localized scleroderma patients., Methods: We analyzed longitudinal data from a single-center cohort of juvenile localized scleroderma patients, using hierarchical generalized linear modeling (HGLM) to identify predictors of QoL impact. HGLM is useful for nested data and allows for evaluation of both time-variant and time-invariant predictors., Results: The number of extracutaneous manifestations (ECMs; e.g., joint contracture and hemifacial atrophy) and female sex predicted negative QoL impact, defined as a Children's Dermatology Life Quality Index score >1 (P = 0.019 for ECMs and P = 0.002 for female sex). As the time since the initial visit increased, the odds of reporting a negative QoL impact decreased (P < 0.001)., Conclusion: Our results suggest that ECMs, sex, and time since initial visit are more predictive of QoL impact in localized scleroderma than cutaneous features. Further study is required to determine which ECMs have the most impact on QoL, which factors underlie sex differences in QoL in localized scleroderma, and why increasing the time since the initial visit appears to be protective. An improved understanding of predictors of QoL impact may allow for the identification of patients at risk of poorer outcomes and for the tailoring of treatment and psychosocial support., (© 2016, American College of Rheumatology.)

Objective: To assess the validity of using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code 710.3 to identify adult patients with dermatomyositis in outpatient and inpatient settings., Methods: Electronic medical records of adult patients with ICD-9 code 710.3 between January 2001 and November 2014 (n = 511) were examined. Physician diagnosis, clinical findings, and diagnostic testing results were recorded. A dermatomyositis rating scale was assigned based on classic cutaneous findings and at least 2 additional clinical and diagnostic findings from the Bohan criteria. Sensitivity and positive predictive values (PPVs) were determined. Sensitivity analyses were performed to evaluate the accuracy of multiple ICD-9 codes in the outpatient setting, as well as primary and secondary inpatient codes., Results: The sensitivity and PPV for multiple 710.3 ICD-9 codes in the outpatient setting were 0.89 and 0.35, respectively. The PPV for primary and secondary 710.3 inpatient codes was 0.95 and as high as 0.8. However, the sensitivity of ICD-9 code 710.3 was poor in the inpatient setting (primary 0.23 and secondary 0.26). The most common reason for failure to meet appropriate dermatomyositis criteria was miscoding as diabetes mellitus (32%), followed by diagnosis at an outside institution (19%), dermatomyositis as a rule-out diagnosis (10%), cutaneous dermatomyositis (8%), and juvenile dermatomyositis (6%)., Conclusion: One or more occurrences of ICD-9 code 710.3 is insufficient to support the diagnosis of dermatomyositis in the outpatient setting. However, ICD-9 710.3 codes appear to be valid in the inpatient setting., (© 2016, American College of Rheumatology.)

Background: Standardized pediatric hospitalist and orthopaedic co-management of spinal fusion patients may improve quality processes and outcomes. This approach has not been studied in a general academic center., Objective: Estimate relative effects and feasibility of the interventions on quality outcomes, length of stay (LOS), catheter-acquired urinary tract infections (CAUTI), medication errors, and pain scores., Design and Setting: Retrospective cohort using interrupted time series, analyzing data from 83 patients aged 5 to 18 years admitted for posterior spinal fusion (PSF) in 2009 (N = 27), 2010 (N = 28), and 2011 (N = 28) on a children's service at a general academic tertiary care center., Interventions: Multimodal approach to standardizing pediatric PSF postoperative care with interdepartmental development of order sets, clinical care guidelines, and routine pediatric hospitalist co-management of all pediatric PSF patients., Measurements: Chi-square analysis of order set use, guideline use measured by proxy medication and documentation data. ANOVA for comparison of CAUTI and medication error rate and multivariate linear regression of LOS and pain scores., Results: Pediatric hospitalist co-management documentation increased from 64% to 80%. Guideline use increased from 40% to 79%, and order set use was < 15%. CAUTI and medication error ratios remained low. Adjusted mean LOS decreased by 0.8 days (p = 0.039, 95% CI 0.7, 1.1). Pain scores did not differ., Conclusion: Interdisciplinary, clinical guideline development and postoperative co-management significantly decreased hospital LOS in pediatric PSF patients. In a general academic medical center, this change may be attributed to a pediatric hospitalist academic team, a universal co-management process with well-communicated roles, and a pediatric hospital-based physician development of and adherence to standardized practice.

Background: The Internet is a significant source of medical information and is now being shown to be an important conduit for delivering various health-related interventions., Objective: This paper aimed to examine the utility and impact of an Internet intervention for childhood encopresis as part of standard medical care in a "real world" setting., Methods: Patients diagnosed with encopresis were given a Web-based information prescription to use an Internet intervention for pediatric encopresis. A total of 22 families utilized the intervention between July 2004 and June 2006. A chart review and phone interview were undertaken to collect user characteristics; defecation-related information, including frequency of soiling, bowel movements (BMs) in the toilet, and amount of pain associated with defecation; and information on computer/Internet usage. Three questionnaires were used to examine the utility of, impact of, and adherence to the Internet intervention. Program utilization was obtained from a data tracking system that monitored usage in real time., Results: Overall, parents rated the Internet intervention as enjoyable, understandable, and easy to use. They indicated that the Internet intervention positively affected their children, decreasing overall accidents and increasing child comfort on the toilet at home. Of the 20 children who initially reported fecal accidents, 19 (95%) experienced at least a 50% improvement, with a reduction of accident frequency from one fecal accident per day to one accident per week. Although it is not clear whether this improvement is directly related to the use of the Internet intervention, patient feedback suggests that the program was an important element, further establishing Internet interventions as a viable and desirable addition to standard medical care for pediatric encopresis., Conclusions: To our knowledge, this is the first time a pediatric Internet intervention has been examined as part of a "real world" setting. This is an important step toward establishing Internet interventions as an adjunctive component to treatment of pediatric patients in a clinical setting, particularly given the positive user feedback, possible cost savings, and significant potential for large-scale dissemination.

5-Fluorouracil (5-FU) is the most routinely administered drug in the treatment of colon cancer. The main mechanism of the drug is not completely understood and its method of administration has been strongly disputed. A 24-hour infusion of 5-FU has clinically yielded better response rates and lower toxicities in comparison to bolus administration, but an exploration into possible mechanisms needs to be performed. Experiments were conducted with two 5-FU resistant cell lines where cytotoxicity, thymidylate synthase (T.S.) activity, thymidine kinase (T.K.) activity, DNA and RNA incorporation, and T.S. expression were contrasted between a 10 microM/24 hour administration of 5-FU (simulating continuous exposure) and a 100 microM/1 hour schedule (simulating bolus administration). After 6 days from the initial exposure, the 10 microM/24 hour schedule (schedule A) inhibited more cell growth than the 100 microM/1 hour regimen (schedule B) by more than 38% and 17% in the two cell lines. After the 6-day observation, schedule A inhibited twice as much T.S. activity as schedule B. Incorporation of [14C]-5-FU into DNA and total RNA was higher in cells exposed to schedule A in comparison to schedule B over the 6 days. T.S. expression and T.K. activity patterns were variable over time. Thus, the exposure of 10 microM/24 hour 5-FU results in superior cytotoxicity when compared to a 100 microM/1 hour regimen and its effectiveness may be explained mechanistically by T.S. activity and DNA and RNA incorporation.

The computer algorithm COMPARE provides information regarding the biological mechanism of action of a compound. In this study, excellent correlations were obtained for 2,2'-[3,3'-dimethoxy[1,1'-biphenyl]-4,4'-diyl)diimino]bis- benzoic acid (redoxal) and 1-(p-bromophenyl)-2-methyl-1H- naphth[2,3-d]imidazole-4,9-dione (BNID) and two well-studied dihydroorotate dehydrogenase (DHOD) inhibitors, dichloroallyl lawsone and brequinar, in terms of antiproliferative activity against tumor cell lines in vitro. When redoxal and BNID were incubated with MOLT-4 cells for 72 hr, 50% growth inhibition was achieved at 0.7 and 3.5 microM, respectively. After 24 hr of incubation, pyrimidine triphosphate pools were shown to be decreased by 50% by redoxal (1 microM) and BNID (0.25 microM). Addition of either uridine (50 microM) or cytidine (100 microM) antagonized the cellular cytotoxicity caused by either drug; uridine corrected the UTP and CTP deficit, whereas cytidine corrected only the CTP deficit. Exposure of MOLT-4 cells to a 1 microM concentration of either drug for 18 hr followed by a 1-hr exposure to [14C]bicarbonate showed a 97% decrease of incorporation of [14C] into pyrimidine triphosphates accompanied by a 91- and 82-fold increase in radioactive incorporation into L-dihydroorotate and N-carbamyl-L-aspartate, respectively. By direct exposure of DHOD prepared from MOLT-4 cell mitochondria to a range of concentrations of the two drugs, apparent Ki values of 0.33 microM (redoxal) and 0.53 microM (BNID) were determined. These data provide direct evidence for inhibition of DHOD by redoxal and BNID in MOLT-4 lymphoblasts.