Amoxicillin did not Reduce Modic Change Oedema in Patients with Chronic Low Back pain - subgroup Analyses of a Randomised Trial (the AIM study)

Study Design. Exploratory subgroup analyses of a randomised trial [Antibiotics in Modic changes (AIM) study]. Objective. The aim was to assess the effect of amoxicillin versus placebo in reducing Modic change (MC) edema in patients with chronic low back pain. Summary of Background Data. The AIM study showed a small, clinically insignificant effect of amoxicillin on pain-related disability in patients with chronic low back pain and MC type 1 (edema type) on magnetic resonance imaging (MRI). Materials and Methods. A total of 180 patients were randomised to receive 100 days of amoxicillin or placebo. MC edema was assessed on MRI at baseline and one-year follow-up. Per-protocol analyses were conducted in subgroups with MC edema on short tau inversion recovery (STIR) or T1/T2-weighted MRI at baseline. MC edema reductions (yes/no) in STIR and T1/T2 series were analyzed separately. The effect of amoxicillin in reducing MC edema was analyzed using logistic regression adjusted for prior disk surgery. To assess the effect of amoxicillin versus placebo within the group with the most abundant MC edema on STIR at baseline (“STIR3” group), we added age, STIR3 (yes/no), and STIR3×treatment group (interaction term) as independent variables and compared the marginal means (probabilities of edema reduction). Results. Compared to placebo, amoxicillin did not reduce MC edema on STIR (volume/intensity) in the total sample with edema on STIR at baseline (odds ratio 1.0, 95% CI: 0.5, 2.0; n=141) or within the STIR3 group (probability of edema reduction 0.69, 95% CI: 0.47, 0.92 with amoxicillin and 0.61, 95% CI: 0.43, 0.80 with placebo; n=41). Compared with placebo, amoxicillin did not reduce MC edema in T1/T2 series (volume of the type 1 part of MCs) (odds ratio: 1.0, 95% CI: 0.5, 2.3, n=104). Edema declined in >50% of patients in both treatment groups. Conclusions. From baseline to one-year follow-up, amoxicillin did not reduce MC edema compared with placebo.publishedVersio

Amoxicillin did not Reduce Modic Change Oedema in Patients with Chronic Low Back pain - subgroup Analyses of a Randomised Trial (the AIM study)

Study Design. Exploratory subgroup analyses of a randomised trial (Antibiotics In Modic changes (AIM) study). Objective. To assess the effect of amoxicillin versus placebo in reducing Modic change (MC) oedema in patients with chronic low back pain (LBP). Summary of Background Data. The AIM study showed a small, clinically insignificant effect of amoxicillin on pain-related disability in patients with chronic LBP and MC type 1 (oedema type) on magnetic resonance imaging (MRI). Methods. A total of 180 patients were randomised to receive 100 days of amoxicillin or placebo. MC oedema was assessed on MRI at baseline and one-year follow-up. Per-protocol analyses were conducted in subgroups with MC oedema on short tau inversion recovery (STIR) or T1/T2-weighted MRI at baseline. MC oedema reductions (yes/no) in STIR and T1/T2-series were analysed separately. The effect of amoxicillin in reducing MC oedema was analysed using logistic regression adjusted for prior disc surgery. To assess the effect of amoxicillin versus placebo within the group with the most abundant MC oedema on STIR at baseline (‘STIR3’ group), we added age, STIR3 (yes/no), and STIR3×treatment group (interaction term) as independent variables and compared the marginal means (probabilities of oedema reduction). Results. Compared to placebo, amoxicillin did not reduce MC oedema on STIR (volume/intensity) in the total sample with oedema on STIR at baseline (odds ratio 1.0, 95% confidence interval (95%CI) [0.5, 2.0]; n=141) or within the STIR3 group (probability of oedema reduction 0.69, 95%CI [0.47, 0.92] with amoxicillin and 0.61, 95%CI [0.43, 0.80] with placebo; n=41). Compared with placebo, amoxicillin did not reduce MC oedema in T1/T2-series (volume of the type 1 part of MCs) (odds ratio 1.0, 95%CI [0.5, 2.3], n=104). Oedema declined in >50% of patients in both treatment groups. Conclusions. From baseline to one-year follow-up, amoxicillin did not reduce MC oedema compared with placebo. Level of Evidence. Level 2

Large herbivores in novel ecosystems - Habitat selection by red deer (<i>Cervus elaphus</i>) in a former brown-coal mining area

<div><p>After centuries of range contraction, many megafauna species are recolonizing parts of Europe. One example is the red deer (<i>Cervus elaphus</i>), which was able to expand its range and is now found in half the areas it inhabited in the beginning of the 19^th century. Herbivores are important ecosystem engineers, influencing e.g. vegetation. Knowledge on their habitat selection and their influence on ecosystems might be crucial for future landscape management, especially for hybrid and novel ecosystems emerging in post-industrial landscapes. In this study, red deer habitat selection was studied in a former brown-coal mining area in Denmark. Here, natural settings were severely changed during the mining activity and its current landscape is in large parts managed by hunters as suitable deer habitat. We assessed red deer habitat preferences through feces presence and camera traps combined with land cover data from vegetation sampling, remote sensing and official geographic data. Red deer occurrence was negatively associated with human disturbance and positively associated with forage availability, tree cover and mean terrain height. Apparently, red deer are capable of recolonizing former industrial landscapes quite well if key conditions such as forage abundance and cover are appropriate. In the absence of carnivores, human disturbance, such as a hunting regime is a main reason why deer avoid certain areas. The resulting spatial heterogeneity red deer showed in their habitat use of the study area might be a tool to preserve mosaic landscapes of forest and open habitats and thus promote biodiversity in abandoned post-industrial landscapes.</p></div

Distribution of sample sites with pellet counts (indicating red deer presence) and without pellet counts (indicating red deer absence) across different categories of the six selected predictor variables.

<p>The bars show the number of sites observed in each category. The white end of each bar shows the proportion of sampled sites with presence of red deer pellets while the black parts depict the proportion of sampled sites with absence of red deer presence. Above each bar the percent of sites in that interval with red deer pellets is shown.</p

Study area, situated in the middle of Jutland (right bottom).

<p>100 circular study sites with a 10 m diameter were randomly distributed over the whole area (left), red points depict findings of pellets in a study site while in orange dots, no pellets were found. Orthophoto printed under a CC BY license, with permission from COWI A/S, Denmark, original copyright 2014 (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0177431#pone.0177431.s005" target="_blank">S1 Text</a>) and ESRI basemaps printed under a CC BY license, with permission from ESRI and its licensors, original copyright 2014 (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0177431#pone.0177431.s006" target="_blank">S2 Text</a>).</p

Deer frequency at camera sites.

<p>Measured as the number of red deer recorded divided by the amount of days the camera recorded (no. deer/day) in sampling sites with or without pellets. A t-test showed a significant difference (p = 0.00351) between the camera recorded activity in sampling sites with no pellets and camera recorded activity in sampling sites with pellets.</p

Example of digitalization of patches of landscape types inside sampling site buffer zones of 100 m radius.

<p>A shows the orthophoto with the buffer zone (red circle) before estimation of the features, and B shows the same buffer zones afterwards (dark green = needle forest, bright green = deciduous forest, blue = lakes, brown = open land, yellow = sand). Orthophoto: 16 cm resolution, printed under a CC BY license, with permission from COWI A/S, Denmark, original copyright 2014 (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0177431#pone.0177431.s005" target="_blank">S1 Text</a>).</p

Logistic regression analysis.

<p>Logistic regression analysis.</p

Clinical effect modifiers of antibiotic treatment in patients with chronic low back pain and Modic changes - secondary analyses of a randomised, placebocontrolled trial (the AIM study)

Background Randomised trials on antibiotic treatment for patients with chronic low back pain and vertebral endplate changes visible on MRI (Modic changes) have shown mixed results. A possible explanation might be a real treatment effect in subgroups of the study populations. The purpose of the present study was to explore potential clinical effect modifiers of 3-months oral amoxicillin treatment in patients with chronic low back pain and type I or II Modic changes at the level of a previous lumbar disc herniation. Methods We performed analyses of effect modifiers on data from AIM, a double-blind parallel-group multicentre trial. One hundred eighty patients with chronic low back pain, previous disc herniation, Modic change type I (n = 118) or type II (n = 62) were randomised to 3-months oral treatment with 750 mg amoxicillin (n = 89) or placebo (n = 91) three times daily. The primary outcome was the Roland-Morris Disability Questionnaire (RMDQ) score (possible values 0–24) at 1-year follow-up in the intention-to-treat population. The predefined minimal clinically important between-group mean difference was 4 RMDQ points (not reached in the primary analysis of AIM). Predefined baseline characteristics were analysed as potential effect modifiers, four primary (type I Modic changes, previous disc surgery, positive pain provocation test, high CRP) and five exploratory (disturbed sleep, constant low back pain, short duration of low back pain, younger age, and male) using ANCOVA with interaction terms. Results None of the four primary potential effect modifiers had strong evidence of modifying the treatment effect. In patients younger than 40 years the difference in mean RMDQ score between the treatment groups was − 4.0 (95%CI, − 6.9 to − 1.2), compared to − 0.5 (95%CI, − 2.3 to 1.3) in patients 40 years or older, both in favour of amoxicillin treatment (exploratory analysis). Conclusions We did not find evidence for convincing clinical effect modifiers of antibiotic treatment in patients with chronic low back pain and Modic changes. Our results for younger age in these explorative analyses should not affect clinical treatment decisions without confirmation in future studies