Rates of hospitalization among patients with deep vein thrombosis before and after the introduction of rivaroxaban

Background. Compared to warfarin, the non-vitamin K antagonist oral anticoagulant rivaroxaban may have advantages in treating patients with venous thromboembolism, because injectable bridging therapy and routine laboratory monitoring are not required. The objective of this study was to compare the rate of hospitalization in patients treated with rivaroxaban after its introduction with what it would have been before the introduction of rivaroxaban. Methods. A retrospective claims analysis was conducted using the MarketScan Hospital Drug Database from January 2011 to December 2013. Adult patients with a primary diagnosis of deep vein thrombosis (DVT) treated with rivaroxaban or low-molecular-weight heparin (LMWH) bridged to warfarin during the first day of an evaluation at a hospital were identified. Based on propensity-score methods, historical LMWH/warfarin patients (i.e., patients who received LMWH/warfarin before the approval of rivaroxaban) were matched 4:1 to rivaroxaban patients, and the rates of hospitalization were compared. Results. All rivaroxaban-treated patients (n = 134) in the database were well matched with four historical LMWH/warfarin-treated patients (n = 536). Among the rivaroxaban cohort, 60% of the patients were admitted to the hospital, compared to 82% of the historical patients treated with LMWH/warfarin in the matched cohort. The difference was statistically significant and corresponded to a 27% reduction in hospital admissions (rate ratio [95% confidence interval]: 0.73 [0.62–0.84]). Hospital admission rates adjusted for time-trend analyses also led to similar results. Conclusion. The availability of rivaroxaban significantly reduced the hospitalization rate in patients with DVT treated with rivaroxaban compared to what it would have been if only LMWH/warfarin were available.     

The VEGFR2, COX‐2 and MMP‐2 polymorphisms are associated with clinical outcome of patients with inoperable non‐small cell lung cancer

Certain common inherited variations in genes involved in tumor angiogenesis, progression and metastasis may contribute to cancer therapy outcome and prognosis by altering the gene expression and protein activity. In this report, we examined the effect of functional polymorphisms in MMP‐1, MMP‐2, MMP‐3, VEGF, VEGFR2, FGFR4 and COX‐2 genes on overall (OS) and progression‐free survival (PFS) of 350 Caucasian patients with inoperable non‐small cell lung cancer (NSCLC). The results of multivariate analysis indicated that VEGFR2 ‐906C and COX‐2 ‐1195G alleles were strongly associated with poor OS and PFS (p = 0.002 and 0.015, respectively, for OS; p = 0.009 and 0.015, respectively, for PFS), while MMP‐2 ‐1306 T allele carriers had significantly reduced PFS (p = 0.010). Moreover, an increased risk of death and progression was significantly associated with the number of adverse alleles for VEGFR2/COX‐2 (p = 0.0005 for OS and 0.0006 for PFS in >1 adverse allele carriers) and VEGFR2/COX‐2/MMP‐2 combinations (p = 0.0003 for OS and 0.0001 for PFS in patients with >2 adverse alleles). Finally, VEGFR2 TC/CC, COX‐2 AG/GG and MMP‐2 CT/TT genotypes as well as “at risk” allele combinations were identified as independent predictors of unfavorable OS and PFS in the group. In conclusion, the data suggest that selected VEGFR2, COX‐2 and MMP‐2 polymorphisms may be potential prognostic markers in unresectable NSCLC treated with radiotherapy with or without chemotherapy, although further validation studies are warranted to confirm our observations.     

DNA strand breaks induced by nuclear hijacking of neuronal NOS as an anti-cancer effect of 2-methoxyestradiol

2-Methoxyestradiol (2-ME) is a physiological metabolite of 17β-estradiol. At pharmacological concentrations, 2-ME inhibits colon, breast and lung cancer in tumor models. Here we investigated the effect of physiologically relevant concentrations of 2-ME in osteosarcoma cell model. We demonstrated that 2-ME increased nuclear localization of neuronal nitric oxide synthase, resulting in nitro-oxidative DNA damage. This in turn caused cell cycle arrest and apoptosis in osteosarcoma cells. We suggest that 2-ME is a naturally occurring hormone with potential anti-cancer properties.     

Quantitative MRI and loss of free ambulation in Duchenne muscular dystrophy

The purpose of this ethics approved trial was to correlate quantitative MRI with functional abilities in both ambulant and non-ambulant Duchenne muscular dystrophy (DMD). Twenty patients with genetically confirmed DMD were recruited. Physical assessment was performed using the motor function measurement (MFM) scale. Axial 3T MRI scans of the thighs were acquired using T1-weighted in- and opposed-phase images (TR = 20 ms, TE₁ = 2.45 ms, TE₂ = 3.68 ms, flip angle = 15°) to calculate the relative fat fraction according to the two-point Dixon method in the knee extensors, flexors, and adductor muscles. The average MFM was 65.3 % and correlated negatively to age (r ² = 0.60). Overall mean fat fraction correlated positively to age (r ² = 0.51–0.64). An average of 5 % increase in mean fat fraction per year was calculated. Mean fat fraction of the quadriceps showed a high negative correlation (r ² = 0.93) to the D1 (standing position and transfers) component of the MFM. A cutoff for mean fat fraction of 50 % predicted loss of ambulation with a sensitivity of 100 % and a specificity of 91 %. Therefore, quantitative muscle MRI seems to be a promising endpoint for short clinical trials evaluating the effect of newer treatments on the time of loss of ambulation in DMD.     

Early identification of Asperger syndrome in young children

This study was designed to identify items of the ADI-R that allow an early and sensitive identification of children with possible Asperger syndrome (AS). The aim was to obtain an economic short interview suitable for screening purposes. The study was based on data from a clinical sample of 5–18-year-old children and adolescents (mean age 10.9 years) with either Attention-Deficit Hyperactivity Disorder (ADHD; n = 43) or AS (n = 62). The introductory questions and 36 items, which contribute to the diagnostic algorithm of the ADI-R, were subjected to content analysis and stepwise discriminant function analysis. Eight meaningful items were found, which were shown to be good predictors of AS and to discriminate between the children with AS and those with ADHD. The short interview was especially useful for the assessment and screening of children up to 11 years in our sample, because in this subgroup, sensitivity was even higher (.92) and specificity was also excellent (.90). Eight items with high discriminatory power allowed sensitive and economic screening for young children with suspected AS.