Evaluation of the long-term efficacy and safety of an imidacloprid 10%/flumethrin 4.5% polymer matrix collar (Seresto®) in dogs and cats naturally infested with fleas and/or ticks in multicentre clinical field studies in Europe

<p>Abstract</p> <p>Background</p> <p>The objective of these two GCP multicentre European clinical field studies was to evaluate the long-term efficacy and safety of a new imidacloprid/flumethrin collar (Seresto^®, Bayer AnimalHealth, Investigational Veterinary Product(IVP)) in dogs and cats naturally infested with fleas and/or ticks in comparison to a dimpylat collar ("Ungezieferband fuer Hunde/fuer Katzen", Beaphar, Control Product (CP)).</p> <p>Methods</p> <p>232 (IVP) and 81 (CP) cats and 271(IVP) and 129 (CP) dogs were treated with either product according to label claims and formed the safety population. Flea and tick counts were conducted in monthly intervals for up to 8 months in the efficacy subpopulation consisting of 118 (IVP) + 47 (CP) cats and 197 (IVP) + 94 (CP) dogs. Efficacy was calculated as reduction of infestation rate within the same treatment group and statistically compared between the two treatment groups.</p> <p>Results</p> <p>Preventive efficacy against fleas in cats/dogs varied in the IVP group between 97.4%/94.1% and 100%/100% (overall mean: 98.3%/96.7%) throughout the 8 month period and in the CP group between 57.1%/28.2% and 96.1%/67.8% (overall mean: 79.3%/57.9%). Preventive efficacy against ticks in cats/dogs varied in the IVP group between 94.0%/91.2% and 100%/100% (overall mean: 98.4%/94.7%) throughout the 8 month period and in the CP group between 90.7%/79.9% and 100%/88.0% (overall mean: 96.9%/85.6%). The IVP group was statistically non-inferior to the CP group, and on various assessment days, statistical superiority was proven for flea and tick count reduction in dogs and cats. Both treatments proved to be safe in dogs and cats with mainly minor local observations at the application site. There was moreover, no incidence of any mechanical problem with the collar in dogs and cats during the entire study period.</p> <p>Conclusions</p> <p>The imidacloprid/flumethrin collar proved to reduce tick counts by at least 90% and flea counts by at least 95% for a period of at least 7-8 months in cats and dogs under field conditions. Therefore, it can be used as sustainable long-term preventative, covering the whole flea and tick season.</p

Risk of Bowel Obstruction in Patients Undergoing Neoadjuvant Chemotherapy for High-risk Colon Cancer

Objective: This study aimed to identify risk criteria available before the point of treatment initiation that can be used to stratify the risk of obstruction in patients undergoing neoadjuvant chemotherapy (NAC) for high-risk colon cancer. Background: Global implementation of NAC for colon cancer, informed by the FOxTROT trial, may increase the risk of bowel obstruction. Methods: A case-control study, nested within an international randomized controlled trial (FOxTROT; ClinicalTrials.gov: NCT00647530). Patients with high-risk operable colon cancer (radiologically staged T3-4 N0-2 M0) that were randomized to NAC and developed large bowel obstruction were identified. First, clinical outcomes were compared between patients receiving NAC in FOxTROT who did and did not develop obstruction. Second, obstructed patients (cases) were age-matched and sex-matched with patients who did not develop obstruction (controls) in a 1:3 ratio using random sampling. Bayesian conditional mixed-effects logistic regression modeling was used to explore clinical, radiologic, and pathologic features associated with obstruction. The absolute risk of obstruction based on the presence or absence of risk criteria was estimated for all patients receiving NAC. Results: Of 1053 patients randomized in FOxTROT, 699 received NAC, of whom 30 (4.3%) developed obstruction. Patients underwent care in European hospitals including 88 UK, 7 Danish, and 3 Swedish centers. There was more open surgery (65.4% vs 38.0%, P=0.01) and a higher pR1 rate in obstructed patients (12.0% vs 3.8%, P=0.004), but otherwise comparable postoperative outcomes. In the case-control–matched Bayesian model, 2 independent risk criteria were identified: (1) obstructing disease on endoscopy and/or being unable to pass through the tumor [adjusted odds ratio: 9.09, 95% credible interval: 2.34–39.66] and stricturing disease on radiology or endoscopy (odds ratio: 7.18, 95% CI: 1.84–32.34). Three risk groups were defined according to the presence or absence of these criteria: 63.4% (443/698) of patients were at very low risk (10%). Conclusions: Safe selection for NAC for colon cancer can be informed by using 2 features that are available before treatment initiation and identifying a small number of patients with a high risk of preoperative obstruction

Common variation near CDKN1A, POLD3 and SHROOM2 influences colorectal cancer risk

We performed a meta-analysis of five genome-wide association studies to identify common variants influencing colorectal cancer (CRC) risk comprising 8,682 cases and 9,649 controls. Replication analysis was performed in case-control sets totaling 21,096 cases and 19,555 controls. We identified three new CRC risk loci at 6p21 (rs1321311, near CDKN1A; P = 1.14 × 10 -10), 11q13.4 (rs3824999, intronic to POLD3; P = 3.65 × 10 -10) and Xp22.2 (rs5934683, near SHROOM2; P = 7.30 × 10 -10) This brings the number of independent loci associated with CRC risk to 20 and provides further insight into the genetic architecture of inherited susceptibility to CRC.</p