Adipose replacement and wall motion abnormalities in right ventricle arrhythmias: evaluation by MR imaging. Retrospective evaluation on 124 patients

We reevaluated the magnetic resonance (MR) examinations of 38 healthy volunteers (control group, CG) and of 124 patients with RV arrhythmia with left bundle branch block (LBBB) morphology: 45 with episodes of RV sustained tachycardia and of polymorphic RV premature beats (RVST-PPB group); 36 with only RV outflow tract sustained or not sustained tachycardia (RVOTT group); 43 with RV monomorphic premature beats (RVMPB group). All the examinations were reevaluated in a blinded fashion for detecting myocardial adipose replacement (AR) and wall bulges or aneurysms. In RVST-PPB patients, no AR was observed in 9%; 1 RV region involvement, 0%; 2 regions, 4%; ≥ 3 regions, 87%; left ventricle (LV), 15%. RVOTT patients: 28%, 53%, 14%, 5%, and 0%, respectively. RVMPB patients: 33%, 46%, 19%, 2%, and 0%, respectively. In CG, AR was observed in 11% (in RV outflow tract). RV bulges were detected in 75% of RVST-PPB , 39% of RVOTT, and 14% of RVMPB patients, none of the CG; RV aneurysms in 33% of RVST-PPB patients, none of RVOTT patients, RVMBP patients, and CG. A significant difference among groups for RV and LV AR as well as RV bulges and aneurysms was found (p < 0.0001). In the direct comparisons, significant differences were found for: disease duration (RVST-PPB vs. RVMPB, p = 0.0396); RV AR (all the patients groups vs. CG, RVST-PPB vs. RVOTT or RVMPB, p < 0.0001); RV aneurysms (RVST-PPB vs. CG. RVST-PPB vs. RVOTT or RVMPB, p < 0.0002); bulges (all comparisons, p < 0.0174). AR is confirmed as a structural substrate in RV arrhythmias. Number and extension of MR abnormalities are correlated to different degrees of RV arrhythmias.     

Intraclass correlation coefficients for cluster randomized trials in primary care: the cholesterol education and research trial (CEART)

Cluster randomization trials are increasingly being used in primary care research. The main feature of these trials is that patients are nested within large clusters such as physician practices or communities and the intervention is applied to the cluster. This study design necessitates calculation of intraclass correlation coefficients in order to determine the required sample size. The purpose of this study is to determine intraclass correlation coefficients for a number of outcome measures at the primary care practice level. The CEART study is a randomized trial testing the effectiveness of translating ATP III guidelines into clinical practice, with primary care physician practices as the unit of randomization and patients as the unit of data collection. The intraclass correlation coefficient (ICC) was<0.02 and the design effect ranged from 1.0 to 2.3, respectively, for weight, total cholesterol, LDL, non-HDL, glucose, creatinine, and % at non-HDL goal. For smoking status, body mass index, systolic blood pressure, HDL cholesterol triglycerides, total cholesterol/HDL ratio and % at LDL goal, the ICC was 0.02-0.047 and the design effect was 2.6-4.1. The largest ICCs (0.05-0.12) and design effects (4.4-9.4) were found for height and diastolic blood pressure. These findings suggest that cluster randomization may substantially increase the sample size necessary to maintain adequate statistical power for selected outcomes such as diastolic blood pressure studies compared with simple randomization for most outcomes evaluated in this study where the design effect is small to moderate. Overall, the ICCs presented will be useful in calculating sample sizes at the primary care level.     

An ontological view of advanced practice nursing

Identifying, developing, and incorporating nursing's unique ontological and epistemological perspective into advanced practice nursing practice places priority on delivering care based on research-derived knowledge. Without a clear distinction of our metatheoretical space, we risk blindly adopting the practice values of other disciplines, which may not necessarily reflect those of nursing. A lack of focus may lead current advanced practice nursing curricula and emerging doctorate of nursing practice programs to mirror the logical positivist paradigm and perspective of medicine. This article presents an ontological perspective for advanced practice nursing education, practice, and research.     

Gene expression signatures in MLL-rearranged T-lineage and B-precursor acute leukemias: dominance of HOX dysregulation

Rearrangements of the MLL locus, located on human chromosome 11q23, are frequent in both infant and therapy-related leukemias. Gene expression analysis of MLL-rearranged B-precursor acute lymphoblastic leukemias (MLL B-ALLs) has identified these cases as a unique subtype of leukemia, characterized by the expression of genes associated with both lymphoid and myeloid hematopoietic lineages. Here we show that MLL fusions also generate a distinct genetic subtype of T-lineage ALL (MLL T-ALL), in which leukemic cells are characterized by an early arrest in thymocyte differentiation, with suggestive evidence of commitment to the gammadelta lineage. Interestingly, multiple genes linked to cell proliferation (eg, PCNA, MYC, CDK2, and POLA) were down-regulated in MLL-fusion samples, relative to those transformed by other T-ALL oncogenes (P <.000 001, Fisher exact test). Overall, MLL T-ALL cases consistently demonstrated increased levels of expression of a subset of major HOX genes--HOXA9, HOXA10, and HOXC6--and the MEIS1 HOX coregulator (P <.008, one-sided Wilcoxon test), a pattern of gene expression that was reiterated in MLL B-ALLs. However, expression of myeloid lineage genes, previously reported in MLL B-ALLs, was not identified in T-lineage cases with this abnormality, suggesting that myeloid gene dysregulation is dispensable in leukemic transformation mediated by MLL fusion proteins. Our findings implicate dysregulation of HOX gene family members as a dominant mechanism of leukemic transformation induced by chimeric MLL oncogenes.     

Tramadol/acetaminophen combination tablets for the treatment of pain associated with osteoarthritis flare in an elderly patient population

OBJECTIVES: To evaluate the efficacy and safety of adding tramadol 37.5 mg/acetaminophen (APAP) 325 mg combination tablets (tramadol/APAP) to existing therapy for painful osteoarthritis (OA) flare in a subset of elderly patients. DESIGN: Randomized, double-blind, placebo-controlled, 10-day add-on study. SETTING: Thirty outpatient centers. PARTICIPANTS: Of 308 patients with painful OA flare, a subset of 113 patients aged 65 and older. MEASUREMENTS: Average daily pain intensity and pain relief scores for Days 1 through 5 and secondary quality-of-life measures and medication assessments. METHODS: Patients received one or two tramadol/APAP tablets or placebo four times per day for 10 days during ongoing nonselective or cyclooxygenase (COX)-2-selective nonsteroidal antiinflammatory drug (NSAID) therapy. RESULTS: Tramadol/APAP (n=69) was significantly superior to placebo (n=44) for average daily pain intensity (P=.034) and pain relief (P=.010) for Days 1 through 5 and Days 1 through 10 (P=.012 and P=.019, respectively). Tramadol/APAP had significantly better investigator (P<.001) and patient (P=.001) overall medication assessments and significantly better scores on three of four Western Ontario and McMaster Universities Osteoarthritis Index measures (P< or =.027). Most common adverse events with tramadol/APAP were nausea (18.8%), vomiting (13.0%), dizziness (11.6%), and constipation (4.3%), with an incidence similar to that of the overall study population. Mean daily dose of tramadol/APAP was 4.5 tablets (168 mg/1,458 mg). CONCLUSION: Tramadol/APAP add-on therapy effectively managed painful OA flare in this elderly subset and was generally well tolerated.     

Ammonia toxicity: Comparative protective effect of various arginine and ornithine derivatives,aspartate, benzoate,and carbamyl glutamate

Ornithine and arginine compounds were highly effective in preventing an increase in blood ammonia and in preventing or minimizing encephalopathy after acute subcoma, comainducing, or lethal doses of NH ₄ ⁺ . Similar protection was seen after subacute loading with glycine. Ornithine ketoacid derivatives were no more effective than ornithine alone or ornithine glutamate. Ornithine appeared to be a little more effective than arginine, but the differences were slight. Aspartate and glutamate alone were ineffective. Carbamyl glutamate was much less effective than either ornithine glutamate or arginine glutamate. Orotic acid excretion was markedly increased in the presence of excess NH ₄ ⁺ . This increment was eliminated with ornithine or arginine, although the reduction with arginine was unpredictably erratic. Aspartate increased the orotic acid excretion and the amount of urea formed. Sodium benzoate was borderline in its effect on the blood ammonia and on orotic acid excretion.     

U.K. utility weights for the EORTC QLU‐C10D

The EORTC QLU‐C10D is a new multi‐attribute utility instrument derived from the widely used cancer‐specific quality of life questionnaire, EORTC QLQ‐C30. It contains 10 dimensions (physical functioning, role functioning, social functioning, emotional functioning, pain, fatigue, sleep, appetite, nausea, bowel problems), each with four levels. The aim of this study was to provide U.K. general population utility weights for the QLU‐C10D. A U.K. online panel was quota‐sampled to align the sample to the general population proportions of sex and age (≥18 years). The online valuation survey included a discrete choice experiment (DCE). Each participant was asked to complete 16 choice‐pairs, each comprising two QLU‐C10D health states plus duration. DCE data were analysed using conditional logistic regression to generate utility weights. Data from 2,187 respondents who completed at least one choice set were included in the DCE analysis. The final U.K. QLU‐C10D utility weights comprised decrements for each level of each health dimension. For nine of the 10 dimensions (all except appetite), the expected monotonic pattern was observed across levels: Utility decreased as severity increased. For the final model, consistent monotonicity was achieved by merging inconsistent adjacent levels for appetite. The largest utility decrements were associated with physical functioning and pain. The worst possible health state (the worst level of each dimension) is ?0.083, which is considered slightly worse than being dead. The U.K.‐specific utility weights will enable cost–utility analysis (CUA) for the economic evaluation of new oncology therapies and technologies in the United Kingdom, where CUA is commonly used to inform resource allocation.