Categorisation of lumbar spine MRI referrals in Denmark as compliant or non-compliant to international imaging guidelines: an inter-rater reliability study.

BACKGROUND: Managing low back pain (LBP) often involves MRI despite the fact that international guidelines do not recommend routine imaging. To allow us to explore the topic and use this knowledge in further research, a reliable method to review the MRI referrals is needed. Consequently, this study aimed to assess the inter-rater reliability of a method evaluating lumbar spine MRI referrals' appropriateness. METHODS: Four inexperienced students (chiropractic master's students) and a senior clinician (chiropractor) were included as independent raters in this inter-rater reliability study. Lumbar spine MRI referrals from primary care on patients (> 18 years) with LBP with or without leg pain were included. The referrals were classified using a modified version of the American College of Radiology (ACR) imaging appropriateness criteria for LBP. Categories of appropriate referrals included; fractures, cancer, previous surgery, candidate for surgery or suspicion of cauda equina. Inappropriate referrals included lacking information on previous non-surgical treatment, no word on non-surgical treatment duration, or "other reasons" for inappropriate referrals. After two rounds of training and consensus sessions, 50 lumbar spine MRI referrals were reviewed independently by the five raters. Inter-rater reliability was quantified using unweighted Kappa statistics, and the observed agreement was calculated with both a pairwise comparison and an overall five-rater comparison. RESULTS: Inter-rater reliability was substantial, with a Kappa value for appropriate vs. inappropriate referrals of 0.76 (95% CI: 0.55-0.89). When six and eight subcategories were evaluated, the Kappa values were 0.77 (95% CI: 0.58-0.91) and 0.82 (95% CI: 0.72-0.92), respectively. The overall percentage of agreement for appropriate and inappropriate referrals was 92% and ranged from 88 to 98% for the pairwise comparisons of the five raters' results. For the six and eight subcategories, the overall agreement was 92 and 88%, respectively, ranging from 88 to 98% and 84-92%, respectively, for the pairwise comparisons. CONCLUSION: The inter-rater reliability of the evaluation of the appropriateness of lumbar spine MRI referrals, according to the modified ACR-appropriateness criteria, was found to range from substantial to almost perfect and can be used for research and quality assurance purposes.

A phase I, open-label study of trebananib combined with sorafenib or sunitinib in patients with advanced renal cell carcinoma.

BACKGROUND: Trebananib, an investigational peptibody, binds to angiopoietin 1 and 2, thereby blocking their interaction with Tie2. PATIENTS AND METHODS: This open-label phase I study examined trebananib 3 mg/kg or 10 mg/kg intravenous (I.V.) once weekly plus sorafenib 400 mg twice per day or sunitinib 50 mg once per day in advanced RCC. Primary end points were adverse event incidence and pharmacokinetics. RESULTS: Thirty-seven patients were enrolled. During trebananib plus sorafenib administration (n = 17), the most common treatment-related adverse events (TRAEs) included rash (n = 12; 71%), diarrhea (n = 12; 71%), hypertension (n = 11; 65%), and fatigue (n = 11; 65%); grade ≥ 3 TRAEs (n = 7; 41%); and 2 patients (12%) had peripheral edema. During trebananib plus sunitinib administration (n = 19), the most common TRAEs included diarrhea (n = 14; 74%), fatigue (n = 13; 68%), hypertension (n = 11; 58%), and decreased appetite (n = 11; 58%); grade ≥ 3 TRAEs (n = 13; 68%); and 8 (42%) patients had peripheral edema. Trebananib did not appear to alter the pharmacokinetics of sorafenib or sunitinib. No patient developed anti-trebananib antibodies. Objective response rates were 29% (trebananib plus sorafenib) and 53% (trebananib plus sunitinib). CONCLUSION: The toxicities of trebananib 3 mg/kg or 10 mg/kg I.V. plus sorafenib or sunitinib in RCC were similar to those of sorafenib or sunitinib monotherapy, with peripheral edema being likely specific to the combinations. Antitumor activity was observed.

Climate-change impacts on hydrology and nutrients in a Danish lowland river basin.

The Mike 11-TRANS modelling system was applied to the lowland Gjern river basin in Denmark to assess climate-change impacts on hydrology and nitrogen retention processes in watercourses, lakes and riparian wetlands. Nutrient losses from land to surface waters were assessed using statistical models incorporating the effect of changed hydrology. Climate-change was predicted by the ECHAM4/OPYC General Circulation Model (IPCC A2 scenario) dynamically downscaled by the Danish HIRHAM regional climate model (25 km grid) for two time slices: 1961-1990 (control) and 2071-2100 (scenario). HIRHAM predicts an increase in mean annual precipitation of 47 mm (5%) and an increase in mean annual air temperature of 3.2 degrees C (43%). The HIRHAM predictions were used as external forcings to the rainfall-runoff model NAM, which was set up and run for 6 subcatchments within and for the entire, Gjern river basin. Mean annual runoff from the river basin increases 27 mm (7.5%, p<0.05) when comparing the scenario to the control. Larger changes, however, were found regarding the extremes; runoff during the wettest year in the 30-year period increased by 58 mm (12.3%). The seasonal pattern is expected to change with significantly higher runoff during winter. Summer runoff is expected to increase in predominantly groundwater fed streams and decrease in streams with a low base-flow index. The modelled change in the seasonal hydrological pattern is most pronounced in first- or second-order streams draining loamy catchments, which currently have a low base-flow during the summer period. Reductions of 40-70% in summer runoff are predicted for this stream type. A statistical nutrient loss model was developed for simulating the impact of changed hydrology on diffuse nutrient losses (i.e. losses from land to surface waters) and applied to the river basin. The simulated mean annual changes in TN loads in a loamy and a sandy subcatchment were, respectively, +2.3 kg N ha(-1) (8.5%) and +1.6 kg N ha(-1) (6.9%). The rainfall-runoff model and the nutrient loss model were chained with Mike 11-TRANS to simulate the combined effects of climate-change on hydrology, nutrient losses and nitrogen retention processes at the scale of the river basin. The mean annual TN export from the river basin increased from the control to the scenario period by 7.7%. Even though an increase in nitrogen retention in the river system of 4.2% was simulated in the scenario period, an increased in-stream TN export resulted because of the simulated increase in the diffuse TN transfer from the land to the surface-waters.