A Randomized Multicenter Phase II Study of Docosahexaenoic Acid in Patients with a History of Breast Cancer, Premalignant Lesions, or Benign Breast Disease.

Obesity, a cause of subclinical inflammation, is a risk factor for the development of postmenopausal breast cancer and is associated with poorer cancer outcomes. Docosahexaenoic acid (DHA), an omega-3 fatty acid, possesses anti-inflammatory properties. We hypothesized that treatment with DHA would reduce the expression of proinflammatory genes and aromatase, the rate-limiting enzyme for estrogen biosynthesis, in benign breast tissue of overweight/obese women. A randomized, placebo-controlled, double-blind phase II study of DHA given for 12 weeks to overweight/obese women with a history of stage I-III breast cancer, DCIS/LCIS, Paget's disease, or proliferative benign breast disease was carried out. In this placebo controlled trial, the primary objective was to determine whether DHA (1,000 mg by mouth twice daily) reduced breast tissue levels of TNFα. Secondary objectives included evaluation of the effect of DHA on breast tissue levels of COX-2, IL1ß, aromatase, white adipose tissue inflammation, and gene expression by RNA-seq. Red blood cell fatty acid levels were measured to assess compliance. From July 2013 to November 2015, 64 participants were randomized and treated on trial (32 women per arm). Increased levels of omega-3 fatty acids in red blood cells were detected following treatment with DHA (P < 0.001) but not placebo. Treatment with DHA did not alter levels of TNFα (P = 0.71), or other biomarkers including the transcriptome in breast samples. Treatment with DHA was overall well-tolerated. Although compliance was confirmed, we did not observe changes in the levels of prespecified biomarkers in the breast after treatment with DHA when compared with placebo. Cancer Prev Res; 11(4); 203-14. ©2018 AACRSee related editorial by Fabian and Kimler, p. 187.

A comparison of the efficacy of three intervention trial types: postal, group, and one-to-one facilitation, prior management and the impact of message framing and repeat messages on the flock prevalence of lameness in sheep.

The aim of this study was to evaluate the effectiveness of three knowledge-transfer intervention trial types (postal, group, one-to-one) to promote best practice to treat sheep with footrot. Further aims were to investigate whether farmer behaviour (i.e. management of lameness) before the trial was associated with uptake of best practice and whether the benefits of best practice framed positively or negatively influenced change in behaviour. The intervention was a message developed from evidence and expert opinion. It was entitled "Six steps to sound sheep" and promoted (1) catch sheep within three days of becoming lame, (2) inspect feet without foot trimming, (3) correctly diagnose the cause, (4) treat sheep lame with footrot or interdigital dermatitis with antibiotic injection and spray without foot trimming, (5) record the identity of treated sheep, (6) cull repeatedly lame sheep. In 2013, 4000 randomly-selected English sheep farmers were sent a questionnaire, those who responded were recruited to the postal (1081 farmers) or one-to-one intervention (32 farmers) trials. A random sample of 400 farmers were invited to join the group trial; 78 farmers participated. A follow-up questionnaire was sent to all participants in summer 2014. There were 72%, 65% and 91% useable responses for the postal, group and one-to-one trials respectively. In both 2013 and 2014, the prevalence of lameness was lower in flocks managed by LC1 farmers than LC2 and LC3 farmers. Between 2013 and 2014, the reduction in geometric mean (95% CI) period prevalence of lameness, proportional between flock reduction in lameness and within flock reduction in lameness was greatest in the one-to-one (7.6% (7.1-8.2%) to 4.3% (3.6-5.0%), 35%, 72%) followed by the group (4.5% (3.9-5.0%) to 3.1% (2.4-3.7%), 27%, 55%) and then the postal trial (from 3.5% (3.3-3.7%) to 3.2% (3.1-3.4%), 21%, 43%). There was a marginally greater reduction in lameness in farmers using most of Six steps but slow to treat lame sheep pre-trial than those not using Six steps at all. There was no significant effect of message framing. The greatest behavioural change was a reduction in therapeutic and routine foot trimming and the greatest attitude change was an increase in negative attitudes towards foot trimming. We conclude that all three intervention trial approaches were effective to promote best practice to treat sheep with footrot with one-to-one facilitation more effective than group and postal intervention trials. Results suggest that farmers' behaviour change was greater among those practising aspects of the intervention message before the trial began than those not practising any aspect.

Associations between sheep farmer attitudes, beliefs, emotions and personality, and their barriers to uptake of best practice: The example of footrot.

There is interest in understanding how farmers' behaviour influences their management of livestock. We extend the theory of planned behaviour with farmers attitudes, beliefs, emotions and personality to investigate how these are associated with management of livestock disease using the example of footrot (FR) in sheep. In May 2013 a one-year retrospective questionnaire was sent to 4000 sheep farmers in England, requesting data on lameness prevalence, management of footrot, farm/flock descriptors, and farmer-orientated themes: barriers to treating footrot, opinions and knowledge of footrot, relating to other people and personality. Principal component analysis (PCA) was used to make composite variables from explanatory variables and latent class (LC) analysis was used to subgroup farmers, based on nine managements of FR. Associations between LC and composite variables were investigated using multinomial logistic regression. Negative binomial regression was used to investigate associations between the proportion of lame sheep and composite and personality variables. The useable response rate was 32% and 97% of farmers reported having lame sheep; the geometric mean prevalence of lameness (GMPL) was 3.7% (95% CI 3.51%-3.86%). Participants grouped into three latent classes; LC1 (best practice-treat FR within 3days of sheep becoming lame; use injectable and topical antibiotics; avoid foot trimming), 11% farmers), LC2 (slow to act, 57%) and LC3 (slow to act, delayed culling, 32%), with GMPL 2.95%, 3.60% and 4.10% respectively. Farmers who reported the production cycle as a barrier to treating sheep with FR were more likely to be in LC2 (RRR 1.36) than LC1. Negative emotions towards FR were associated with higher risk of being in LC2 (RRR 1.39) than LC1. Knowledge of preventing FR spread was associated with a lower risk of being in LC2 (RRR 0.46) or LC3 (RRR 0.34) than LC1. Knowledge about FR transmission was associated with a lower risk of being in LC3 (RRR 0.64) than LC1. An increased risk of lameness was associated with the production cycle being a barrier to treating sheep with FR (IRR 1.13), negative emotions towards FR (IRR 1.13) and feelings of hopelessness towards FR (IRR 1.20). Conscientiousness (IRR 0.95) and understanding the importance of active control of lameness (IRR 0.76) were associated with reduced risk of lameness. We conclude that emotions and personality are associated with differences in farmer management of FR and prevalence of lameness. Further understanding how personality and emotions influence change in behaviour is key to increasing uptake of new information.

Factors associated with the presence and prevalence of contagious ovine digital dermatitis: A 2013 study of 1136 random English sheep flocks.

In 2013, a questionnaire was used to gather data on risks for introduction, and factors associated with prevalence, of contagious ovine digital dermatitis (CODD). There were 1136 (28.4%) usable responses from 4000 randomly selected sheep farmers in England. CODD was present in 58% (662) of flocks, with a reported prevalence of CODD lesions of 2.3%. The geometric mean period prevalence of all lameness was 4.2% and 2.8% in CODD positive and negative flocks respectively. Factors associated with a greater risk of presence of CODD were purchasing replacement ewes, not always checking the feet of sheep before purchase, not isolating purchased sheep, foot bathing returning ewes, foot trimming the flock more than twice in the year all compared with not doing these activities and increasing log10 flock size. Farmers who vaccinated sheep with Footvax™ were less likely to report presence of CODD. Factors associated with increasing prevalence of CODD lesions were not always checking the feet of purchased sheep, flocks that mixed with other flocks and sheep that left the farm for summer grazing and later returned. In addition, flocks where farmers followed the current recommended managements for control of footrot, had a lower prevalence of CODD whilst those who used foot bathing and where feet bled during routine foot trimming had a higher prevalence of CODD. The prevalence of CODD decreased with each log10 increase in flock size. We conclude that CODD is an infectious cause of lameness in sheep of increasing importance in GB. Introduction is linked to poor biosecurity with one likely source of the pathogen being introduction of or mixing with infected sheep. As with footrot, prevalence of CODD was lower in flocks where farmers focused on individual treatment to manage lameness and avoided foot bathing and trimming feet. We conclude that most of the currently recommended biosecurity and treatment approaches to control footrot in GB are also effective for control of CODD.

Inadvertent use of aromatase inhibitors in patients with breast cancer with residual ovarian function: cases and lessons.

Aromatase inhibitors (AIs) are important adjunctive therapy for postmenopausal women with hormone receptor-positive, early-stage breast cancer. At the present time, AIs have no role for the management of breast cancer in premenopausal women. We report on several cases of the inadvertent use of AI therapy among women with residual ovarian function. A common experience in these cases was the onset of chemotherapy-related amenorrhea before initiation of AI therapy, which confounded assessment of true menopausal status. We believe clinicians should be aware of the potential ovarian reserve among women with treatment-related amenorrhea so as to avoid use of AI therapy in patients in whom there is uncertainty about menopausal status.