Assessing adherence to objective disease monitoring and outcomes with adalimumab in a real-world IBD cohort.

BACKGROUND: Data suggests that tight objective monitoring may improve clinical outcomes in IBD. AIM: To assess the adherence to serial tight objective monitoring(clinical and biomarkers) and its effect on clinical outcomes. METHODS: We retrospectively reviewed the chart of 428 consecutive IBD patients started on adalimumab between January 1,2015-January 1,2019 [338 Crohn's disease(CD), 90 ulcerative colitis(UC)]. Clinical symptoms(assessed by Harvey-Bradshaw-Index,partial Mayo),C-Reactive Protein(CRP), and fecal calprotectin(FCAL) assessments were captured at treatment initiation and at 3,6,9, and12 months. Dose optimization and drug sustainability curves were plotted by Kaplan-Meier method. RESULTS: Clinical evaluation was available in nearly all patients at 3(CD-UC:95-94%), 6(90-83%), 9(86-85%) and 12(96-89%) months. CRP testing frequency decreased in CD patients over time. Compliance to serial FCAL testing was low. Clinical remission at one-year was higher in patients adherent to early assessment visit at 3 months(p = 0.001 for CD and UC). Adherence to early follow-up resulted in earlier dose optimization in CD and UC patients(pLogrank=0.026 for UC & p = 0.09 for CD). Overall drug sustainability did not differ. CONCLUSION: Clinical & CRP, but not FCAL, were frequently assessed in patients starting adalimumab. Adherence to early objective combined follow-up visits resulted in earlier dose optimization, improved one-year clinical outcomes but did not change drug sustainability.

Cost-benefit of implementing a participatory extension model for improving on-farm adoption of Johne's disease control recommendations.

The objective of this study was to perform a cost-benefit analysis (CBA) of a participatory extension model, called Ontario Focus Farms (FF), which was designed to facilitate the adoption of on-farm management practices to control Johne's disease (JD) on Ontario (ON) dairy farms. Partial budget models were developed to estimate the annual herd cost of JD on an average 78-cow Ontario dairy herd and the annual herd cost of neonatal calf diarrhea (NCD). With these estimates, a CBA was developed to assess the simulated net benefits of implementing various on-farm management scenarios (i.e., implementing 1, 2, or 3 of the following: calf feeding, maternity pen management, maternity area structure changes), where the benefits represent a reduction in the annual cost of JD and NCD. These models informed the final CBA assessing the net benefits of FF implementation over a 10-yr period. All monetary values are reported in Canadian dollars (Can$; where 1 Can$ = 0.823 US$ at the time of the study). The annual herd cost of JD was estimated to be $3,242 ($41.56/cow), and that of NCD was estimated to be $1,390 ($36/heifer calf). When farms were expected to have both JD and NCD, all scenarios, when implemented over a 10-yr period, yielded positive net benefits ranging from $439 to $2,543 per farm when changes to maternity area structure were combined with calf feeding changes. These effects were sensitive to changes in level of disease (JD and NCD) on the farm, and the costs and effects of making changes. The NPV of making any on-farm change when JD was not present on the farm was negative. Overall, FF implementation yielded positive net benefits of $426,351 or $749,808, depending on whether a veterinarian or non-veterinarian served as the facilitator. The NPV was most sensitive to changes in burden of disease, the cost of implementing changes, and the proportion of FF participants that had JD and NCD on the farm. Benefits of FF implementation are also likely to accrue to veterinarians, as a result of professional facilitator training, and the Ontario dairy industry, as a by-product of improved milk quality and safety; therefore, the true net benefits of FF implementation are likely underestimated. Overall, the FF process should be considered an economically viable program and worthy of investment as part of a JD control strategy, as it demonstrates potential to yield positive net benefits for the Ontario dairy industry.

Canadian association of gastroenterology clinical practice guideline for the management of Luminal Crohn's Disease

Crohn's disease (CD) is a lifelong illness with substantial morbidity, although new therapies and treatment paradigms have been developed. We provide guidance for treatment of ambulatory patients with mild to severe active luminal CD. We performed a systematic review to identify published studies of the management of CD. The quality of evidence and strength of recommendations were rated according to the Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach. Statements were developed through an iterative online platform and then finalized and voted on by a group of specialists. The consensus includes 41 statements focused on 6 main drug classes: antibiotics, 5-aminosalicylate, corticosteroids, immunosuppressants, biologic therapies, and other therapies. The group suggested against the use of antibiotics or 5-aminosalicylate as induction or maintenance therapies. Corticosteroid therapies (including budesonide) can be used as induction, but not maintenance therapies. Among immunosuppressants, thiopurines should not be used for induction, but can be used for maintenance therapy for selected low-risk patients. Parenteral methotrexate was proposed for induction and maintenance therapy in patients with corticosteroid-dependent CD. Biologic agents, including tumor necrosis factor antagonists, vedolizumab, and ustekinumab, were recommended for patients failed by conventional induction therapies and as maintenance therapy. The consensus group was unable to clearly define the role of concomitant immunosuppressant therapies in initiation of treatment with a biologic agent. Optimal management of CD requires careful patient assessment, acknowledgement of patient preferences, evidence-based use of existing therapies, and thorough assessment to define treatment success.

A qualitative study of Ontario dairy farmer attitudes and perceptions toward implementing recommended milking practices.

Recommended milking practices (RMP) are protective against mastitis. However, many producers do not adopt, or only partially adopt, these measures. This study aimed to explore the attitudes and perceptions of Ontario dairy farmers toward barriers to implementation of RMP and to investigate what motivates behavior change in relation to milking hygiene. Four focus groups with Ontario dairy producers were conducted, and verbatim transcripts were analyzed thematically. The main barriers to adoption of RMP were identified and categorized into 2 groups: intrinsic barriers and physical barriers. Intrinsic barriers included personal habits and convenience, not perceiving udder health as a priority on their farm, and lack of information. Physical barriers included employee training and compliance, convenience of implementing RMP, and time, money, and labor barriers. Producers used their bulk tank somatic cell count (SCC) as a measure of perceived severity of udder health problems on farm. Those with lower SCC were less likely to prioritize udder health compared with peers experiencing elevations in SCC. Lack of udder health problems translated for some producers into non-adoption of certain RMP, as they felt these practices were not needed unless a problem arose. Others felt motivated to implement more practices and work toward better udder health if such efforts translated into rewards for better-quality milk. Some producers perceived RMP as not meaningful or useful, seemingly due to a lack of education about the reasons behind RMP implementation. Understanding the importance of these practices is one key to implementing them. To overcome some of the intrinsic barriers, increased efforts in knowledge translation are needed, including efforts in retraining current practices, as well as in establishing best practices.

Exploring dairy producer and veterinarian perceptions of barriers and motivators to adopting on-farm management practices for Johne's disease control in Ontario, Canada.

Motivating uptake of management change recommendations requires knowledge of the barriers and motivators influencing producer behavior. This study investigated dairy producers' and veterinarians' perceptions of the barriers and motivators influencing the adoption of Johne's disease (JD) control recommendations in Ontario, Canada. Eight focus groups, 6 with dairy producers and 2 with veterinarians, were conducted and thematically analyzed. Both producer and veterinarian groups identified physical resources (i.e., time, money, infrastructure) and producer mindset (i.e., perceived priority of JD, perceived practicality of JD control recommendations) as key barriers to adoption. Producers tended to prioritize JD control on their farm based on their lived experiences with JD and their view of the public's concern about JD. Many agreed that JD recommendations should focus on biosecurity more holistically and emphasize the broader health benefits of limiting calf exposure to many fecal-orally transmitted diseases. Producers also highlighted that some recommendations for on-farm change (i.e., keeping a closed herd, buying from low-risk herds) were unrealistic or too difficult to perform and often disrupted their habits or routine. In contrast, veterinarians suggested that most recommendations were practical and are routinely recommended. Participants suggested both extrinsic (i.e., incentives, premiums, penalties and regulations, and extension and communication) and intrinsic (i.e., pride and responsibility) methods for motivating producers. This study highlights the importance of producer mindset in on-farm change and offers insights into the attitudes and perceived barriers influencing on-farm change.

Dairy producers' attitudes toward reproductive management and performance on Canadian dairy farms.

The objectives of this study were to explore Canadian dairy producers' attitudes toward reproductive performance and challenges they perceive to be related to reproduction and reproductive management practices. A survey in both English and French was developed, validated, and administered to Canadian dairy farmers between March and May 2014 to collect general farm, reproduction management, and reproductive performance data, as well as opinions and perceptions about different facets of reproduction. Associations between management practices and the perceived importance of reproduction were tested using a logistic regression model. Thematic network analysis was used to identify themes from the open-ended survey questions about challenges concerning reproduction. Finally, questions that were answered on a Likert scale were graphically represented using diverging stacked bar charts. A total of 832 questionnaires were completed online and by mail, which represents approximately 7% of all dairy farms in Canada. Respondents that ranked reproduction in lactating dairy cows as 1 of the 3 most important challenges faced on their farm (66%) were more likely to house their lactating cows in a tiestall and to have a lower herd annual 21-d pregnancy rate. Estrus detection and conception risk were 2 major themes raised and discussed by the respondents. Other concepts, including housing and milk production, were also perceived to affect estrus detection and conception risk. Whereas analysis of open-ended survey questions does not allow for quantification of the importance of different themes in the sample as a whole, it does show that respondents are aware of the multifactorial complexity of reproductive challenges on dairy farms. Improving performance was the main factor influencing decisions concerning reproduction for 80% of the respondents, and they adopted tools and technologies such as synchronization programs and automated activity monitoring systems to improve herd reproductive performance. More research is required to describe how this performance is defined and perceived by the respondents, and how it relates to the actual variability of performance (i.e., pregnancy rate) among farms.

Performance of automated activity monitoring systems used in combination with timed artificial insemination compared to timed artificial insemination only in early lactation in dairy cows.

Identifying cows in estrus remains a challenge on dairy cattle farms, and tools and technologies have been developed and used to complement or replace visual detection of estrus. Automated activity monitoring (AAM) systems and timed artificial insemination (TAI) are technologies available to dairy farmers, but many factors can influence their relative performance. The objective of the present study was to compare reproductive performance of cows managed with an AAM system combined with TAI, or with a TAI program (Double Ovsynch) for insemination before 88 DIM. From April 2014 to April 2015, 998 cows from 2 herds were randomly assigned either to be inseminated at 85 ± 3 DIM exclusively using the Double Ovsynch protocol for TAI, or to be inseminated based on estrus detection by AAM without hormonal intervention between 50 and 75 DIM; if no alarm was detected by 75 DIM, cows were inseminated following the single Ovsynch protocol (AAM + Ovsynch). The herds used different AAM systems. Parity, hyperketonemia at wk 1 and 2 postpartum (PP), purulent vaginal discharge at wk 5 PP, body condition score at wk 7 PP, and anovulation to wk 9 PP were recorded. These health indicators did not significantly differ between treatments, but did between herds. The effect of treatment on pregnancy at first insemination and by 88 DIM were assessed using logistic regression models. Time to pregnancy was assessed using survival analysis. Results are reported from intention-to-treat analyses. Treatment did not affect pregnancy at first insemination or pregnancy by 88 DIM, but we found significant interactions between treatment and herd for both outcomes. In herd 2, marginal mean pregnancy at first AI was greater with Double Ovsynch (38%) than AAM + Ovsynch (31%), but no difference was observed in herd 1 (Double Ovsynch = 31%; AAM + Ovsynch = 34%). By 88 DIM, a smaller proportion of cows in herd 1 were pregnant in Double Ovsynch (31%) than AAM + Ovsynch (49%), but there was no difference in herd 2 (Double Ovsynch = 38%; AAM + Ovsynch = 38%). We observed a treatment by herd interaction for median (95% confidence interval) time to pregnancy, which were, in herd 1, 110 (106 to 129) and 98 (88 to 113) d, and, in herd 2, 126 (113 to 139) and 116 (105 to 131) d for the Double Ovsynch and AAM + Ovsynch treatments, respectively. The relative performance of AAM-based reproductive management compared with TAI only is likely influenced by herd-specific variables, in particular related to insemination rate when estrus detection is employed.

What's in a Name? The Incorrect Use of Case Series as a Study Design Label in Studies Involving Dogs and Cats.

BACKGROUND: Study design labels are used to identify relevant literature to address specific clinical and research questions and to aid in evaluating the evidentiary value of research. Evidence from the human healthcare literature indicates that the label "case series" may be used inconsistently and inappropriately. OBJECTIVE: Our primary objective was to determine the proportion of studies in the canine and feline veterinary literature labeled as case series that actually corresponded to descriptive cohort studies, population-based cohort studies, or other study designs. Our secondary objective was to identify the proportion of case series in which potentially inappropriate inferential statements were made. DESIGN: Descriptive evaluation of published literature. PARTICIPANTS: One-hundred published studies (from 19 journals) labeled as case series. METHODS: Studies were identified by a structured literature search, with random selection of 100 studies from the relevant citations. Two reviewers independently characterized each study, with disagreements resolved by consensus. RESULTS: Of the 100 studies, 16 were case series. The remaining studies were descriptive cohort studies (35), population-based cohort studies (36), or other observational or experimental study designs (13). Almost half (48.8%) of the case series or descriptive cohort studies, with no control group and no formal statistical analysis, included inferential statements about the efficacy of treatment or statistical significance of potential risk factors. CONCLUSIONS: Authors, peer-reviewers, and editors should carefully consider the design elements of a study to accurately identify and label the study design. Doing so will facilitate an understanding of the evidentiary value of the results.

Adoption and consistency of application of premilking preparation in Ontario dairy herds.

Milking management practices that affect udder health have been widely studied, leading to a variety of evidence-based recommendations. Lack of adoption or inconsistency in milking practices can interfere with efforts to prevent mastitis in the herd. The study objective was to assess the variation in adoption and application consistency of important milk harvest practices between and within farms over time. During the summer of 2013, 50 herds in southern Ontario were visited twice within a month, at milking time, and a single person observed and time-recorded premilking preparation procedures. A generalized mixed model was used to partition the variance for predisinfectant contact time and preparation lag time (time between the first contact with the teats and cluster attachment), and determine the proportion of variation attributable to farms, milkers, visits, and characteristics of a cow milking. Using logistic regression, models were built to assess factors affecting adequate contact time and adequate preparation lag time, respectively. Farm, the person(s) milking, and visit number were used as random effects in both instances. In both models, farm-to-farm differences and variations between cows during a specific milking accounted for the largest part of the variability seen in both contact time (47 and 44%, respectively) and preparation lag time (40 and 36%, respectively). For both outcomes, milkers were consistent in their routines over the 2 visits (only 9 and 3.1% of total variance for contact and preparation lag time, respectively). Parlors were more likely to meet the recommended contact time than tie-stalls; increased number of milkers at milking time and having contact times under 30 s had negative effects on meeting recommended preparation lag time. The majority of farms in the study complied with the recommendations for adequate milking practices; however, most did not follow a consistent timed protocol. There are several potential sources of variation in the milking routine on a dairy farm. To improve milk quality and udder health, it is important to identify whether best management practices are being implemented on each farm. Producers appeared to be consistent in the application of milking procedures across time, regardless of whether or not they were correct. Hence, with corrective education and training, improvements in these practices could be experienced and maintained to promote better udder health.

The Canadian National Dairy Study 2015-Adoption of milking practices in Canadian dairy herds.

Several studies have investigated which management practices have the greatest effect on udder health, but little information is available on how broadly the recommended milking practices are adopted across Canada. The National Dairy Study 2015 was designed to gather dairy cattle health and management data on dairy farms across Canada. The objectives of the present study were to describe the current proportions of adoption of milking practices on Canadian dairy farms, and identify factors associated with their use on farms. A bilingual questionnaire measuring use of various practices, including an udder health-specific section, was developed and sent to all Canadian dairy farms. The questions in the udder health section of the questionnaire were adapted from a bilingual questionnaire previously validated and containing questions regarding general milking hygiene and routine, and on-farm mastitis management. Chi-squared tests were used to investigate simple associations between adoption of practices and various explanatory variables including region, milking system, herd size, and bulk tank somatic cell count. In total, 1,373 dairy producers completed the survey. The regional distribution of the participants was representative of the Canadian dairy farm population, and milk quality was, on average, similar to nonparticipants. Overall, Canadian dairy producers followed the recommendations for milking procedures, but some were more extensively used than others. Fore-stripping, cleaning teats, wiping teats dry, using single-cow towels, and use of postmilking teat disinfectant were widely adopted. Use of gloves and glove hygiene, use of a premilking teat disinfectant, and use of automatic takeoffs were not as extensively implemented. Adoption percentages for several practices, including use of gloves, use of a premilking teat disinfectant, teat drying methods, and use of automatic takeoffs were significantly associated with milking system, herd size, and region. It would be helpful to explore the reasons why producers choose to adopt or ignore recommended milking practices as most are easy to include in the routine and are fairly inexpensive.

Cross-reactivity between annexin A2 and Beta-2-glycoprotein I in animal models of antiphospholipid syndrome.

Antiphospholipid syndrome (APS) affects coagulation and the brain by autoimmune mechanisms. The major antigen in APS is beta-2-glycoprotein I (ß2-GPI) is known to complex with annexin A2 (ANXA2), and antibodies to ANXA2 have been described in APS. We measured these antibodies in mice with experimental APS (eAPS) induced by immunization with ß2-GPI. Sera of these mice reacted significantly with recombinant ANXA2 by enzyme-linked immunosorbent assay (ELISA) and the eAPS mice had significantly high levels of immunoglobulin G (IgG) in the brain by immunoblot assays compared to adjuvant immunized controls. Immunoprecipitation performed by mixing eAPS brain tissue with protein-G beads resulted in identification of two autoantigens unique to the eAPS group, one of which was ANXA2. In order to study more directly and methodically the specific role of anti-ANXA2 antibodies in APS, we immunized mice with ß2-GPI which contained no ANXA2 or with ANXA2 and measured antibodies to these proteins. Levels of antibodies to ANXA2 measured by ELISA were 0.72 ± 0.007 arbitrary units (a.u), 0.24 ± 0.03 and 0.02 ± 0.01 a.u for sera from ANXA2, ß2-GPI and control mice, respectively (p < 0.0001 and p = 0.037 for the comparison of the ANXA2 and ß2-GPI groups to the controls). Purified IgG from ß2-GPI sera did not show cross-binding with ANXA2. Antibodies to ß2-GPI and phospholipids were found in the ß2-GPI immunized group only. The present study suggests an immune response to the ß2-GPI-ANXA2 complex in eAPS and provides a novel ANXA2 immunization model which will serve to study the role of ANXA2 antibodies in of APS.

Identification of effective treatment criteria for use in targeted selective treatment programs to control haemonchosis in periparturient ewes in Ontario, Canada.

Haemonchosis is often associated with late gestation and parturition in ewes in Canada. Due to widespread concerns about development of anthelmintic resistance (AR), targeted selective treatment (TST), where individual animals are treated with an anthelmintic rather than the entire flock, is a possible strategy to control clinical signs in recently lambed ewes while still maintaining parasite refugia. Performing fecal egg counts (FEC) on individual animals is often cost-prohibitive, so indicators that identify ewes with high FEC are essential for TST programs. The study objectives were to: a) evaluate the ability of four TST indicators to identify periparturient ewes with high Haemonchus sp. FEC and b) determine appropriate treatment thresholds for statistically-significant indicators. A field study was conducted during the 2013 and 2014 lambing seasons (February-May) on three client-owned farms in Ontario with documented AR and problems with haemonchosis in ewes. Ewes were examined within three days of lambing and selected for treatment with oral closantel (10mg/kg body weight), a novel anthelmintic to Canada, if they met at least one of four criteria: a) the last grazing season was their first grazing season; b) body condition score ≤2; c) Faffa Malan Chart (FAMACHA©) score ≥3; and/or d) three or more nursing lambs. Fecal samples were collected per rectum on the treatment day from each of 20 randomly selected treated and untreated ewes on each farm. Haemonchus sp. percentages on each farm, as determined by coproculture, ranged from 53% to 92% of total fecal trichostrongyle-type egg counts. Mean Haemonchus sp. FECs were significantly higher in treated ewes (n=136) than in untreated ewes (n=103) on the day of treatment in both years (p=0.001), suggesting the indicators were suitable for identifying animals with high Haemonchus sp. FEC. A linear mixed model was fit with logarithmic-transformed Haemonchus sp. FEC as the outcome variable, the four indicators and year as fixed effects, and farm as a random effect. FAMACHA© score was the sole indicator to remain significantly associated with FEC (p=0.002). A receiver-operator curve determined that test sensitivity was maximized (92.4%) with FAMACHA© score ≥3 as the sole indicator. FAMACHA© score should therefore be included in TST programs to identify ewes requiring treatment at lambing due to Haemonchus sp.

Efficacy of closantel against ivermectin- and fenbendazole-resistant Haemonchus sp. in sheep in Ontario, Canada.

In Ontario, Canada, widespread resistance to ivermectin and fenbendazole, the only readily available ovine anthelmintics, has been documented, primarily in Haemonchus sp. In other parts of the world, closantel has been used to control such infections; however, the drug was not currently licensed for use in Canada and the USA. A randomized controlled trial was conducted on six client-owned farms in Ontario in 2013 and 2014 to determine the efficacy of closantel (Flukiver® 5% Oral Suspension, Elanco Animal Health, 10mg/kg bodyweight) against ivermectin- and fenbendazole-resistant Haemonchus sp. infections in periparturient ewes and grazing lambs. Three farms were randomly assigned to treat all ewes, and three farms were randomly assigned to selectively treat individual ewes at lambing, using predetermined criteria. Fecal samples were collected from a minimum of 15 randomly selected ewes and 13 lambs per group on each farm at the time of treatment and approximately 14days later. Trichostrongyle-type fecal egg counts (FEC) were performed using a modified McMaster technique with a lower detection limit of 8.3 eggs per gram of feces (epg). Haemonchus-specific FECs were determined by multiplying FECs by the proportion of Haemonchus sp. identified from coproculture for each farm; Haemonchus-specific FEC reductions were calculated for each farm. Twenty grazing lambs had FECs conducted monthly, and when mean monthly FECs surpassed 200 epg, all lambs were randomly allocated to either closantel, positive control (ivermectin, fenbendazole, or levamisole) or negative control groups. Pre-treatment Haemonchus-specific mean FECs ranged from 27 to 3359 epg in ewes and 0-5698 epg in lambs. Efficacy of closantel against Haemonchus sp. ranged from 99% (95% CI: 97%-99%) to 100% in recently lambed ewes on all farms in both years (total n=274 ewes), and from 99% (95% CI: 98%-99%) to 100% in grazing lambs in both years on all but one farm (total n=171 lambs). On the latter farm, a whole flock treated farm, closantel efficacy in grazing lambs was 84% (95%CI: 81%-88%) in the first year, but 100% in the second year. Levamisole was effective against overall GIN in lambs on only two farms. Ivermectin and fenbendazole resistance continued to be present, particularly in Haemonchus sp. Closantel had excellent efficacy against Haemonchus sp. over the two year study period, regardless of treatment group, and therefore should be considered one viable component of sustainable integrated parasite control programs for farms with documented anthelmintic resistance and problems with haemonchosis.

Survey of reproduction management on Canadian dairy farms.

The objectives of this study were to (1) quantify current reproduction management practices, and (2) assess the association between these practices and herd reproductive performance on dairy farms in Canada. A bilingual survey was developed, validated, and administered from March to May 2014 to collect general and reproduction management and performance measures [annual 21-d pregnancy rate (PR), 21-d insemination rate (IR), and conception risk (CR)]. Associations between management practices and reproductive performance measures were tested using linear regression models. A total of 832 questionnaires were completed online and by mail, representing a response rate of 9%. On average, farms had 77 lactating cows (median=50) and 13 dry cows (median=10), and Holstein was the most common breed (92% of herds). Lactating cow housing was tiestall on 61% of the farms, freestall on 37%, and bedded pack on 2%. The average voluntary waiting period was 58 d in milk (DIM). The main reproduction management practice per farm was defined as the means employed for >50% of inseminations. Farms reported their main reproduction management practice for first and subsequent inseminations, respectively, as visual estrus detection (51 and 44% of herds), timed AI (21 and 23% of herds), automated activity monitoring (AAM; 10 and 10% of herds), other management practice (bulls; 2 and 2% of herds), and a combination of management practices (16 and 21% of herds). On farms using visual estrus detection, cows were observed for signs of estrus on average 3.5 times per day, for an average total of 36 min/d. The most common use of reproductive hormones was to synchronize ovulation using Ovsynch (58% of the farms). Average PR, IR, and CR were 17.6, 44.1, and 40.5%, respectively. In linear regression analyses adjusted for confounders, pregnancy rate was significantly associated with geographic region, housing (tiestall: PR=15.4%, freestall: PR=17.6%), herd size (<50 lactating cows: PR=16.2%, 50-100 cows: PR=16.5%, >100 cows: PR=17.8%), voluntary waiting period (≤60 DIM: PR=17.6%, >60 DIM: PR=15.9%), and frequency of insemination per day (once daily: PR=16.6%, twice or more daily: PR=18.1%). The main reproduction management practice at first and subsequent inseminations was divergently associated with IR and CR, but not with PR (visual heat detection: PR=17.4%, timed AI: PR=18.4%, AAM: PR=17.1%, combined practices: PR=18.2%).

Annexin A2, autoimmunity, anxiety and depression.

OBJECTIVES: Antiphospholipid syndrome (APS) is associated with neurological manifestations and one of the novel autoantigens associated with this disease is Annexin A2 (ANXA2). In this work we have examined the effect of high levels of autoantibodies to ANXA2 on the brain in a mouse model. METHODS: Recombinant ANXA2 emulsified in adjuvant was used to immunize mice while mice immunized with adjuvant only served as controls. At peak antibody levels the animal underwent behavioral and cognitive tests and their brains were examined for ANXA2 immunoglobulin G (IgG) and expression of ANXA2 and the closely linked protein p11. RESULTS: Very high levels of anti-ANXA2 antibodies (Abs) were associated with reduced anxiety in the open field 13.14% ± 0.89% of the time in the center compared to 8.64% ± 0.91% observed in the control mice (p < 0.001 by t-test). A forced swim test found significantly less depression manifested by immobility in the ANXA2 group. The changes in behavior were accompanied by a significant reduction in serum corticosteroid levels of ANXA2 group compared to controls. Moreover, higher levels of total IgG and p11 expression were found in ANXA2 group brains. Lower levels of circulating anti-ANXA2 Abs were not associated with behavioral changes. CONCLUSIONS: We have established an animal model with high levels of anti-ANXA2 Abs which induced IgG accumulation in the brain and specific anxiolytic and anti-depressive effects. This model promises to further our understanding of autoimmune disease such as APS and to provide better understanding of the role of the ANXA2-p11 complex in the brain.

Coxiella burnetii seropositivity and associated risk factors in sheep in Ontario, Canada.

Coxiella burnetii is a zoonotic bacterium that can cause abortion in sheep in late gestation, as well as the delivery of stillborn, and non-viable lambs (Rodolakis, 2006). A cross-sectional study was conducted in Ontario, Canada, to investigate C. burnetii exposure in sheep. Between August 2010 and January 2012, sera from 2363 reproductively active ewes from 72 farms were tested for C. burnetii specific antibodies using the CHEKIT Q fever ELISA Test kit (IDEXX Laboratories). Overall, exposure was common; sheep-level seroprevalence was 14.7% (347/2363, 95% CI: 13.3-16.2), and was higher in dairy sheep (24.3%, 181/744) than meat sheep (10.2%, 166/1619) (p<0.0001). At the farm-level, 48.6% (35/72, 95% CI: 37.2-60.1) of farms had at least one seropositive sheep. A mixed multivariable logistic model that controlled for farm-level clustering, identified risk factors associated (p<0.05) with sheep seropositivity. Increasing female flock size (logarithmic scale) was associated with increased odds of seropositivity. By way of illustration, increasing the female flock size from 100 to 200 increased the odds of seropositivity by 2.26 times (95% CI: 1.5-3.5). Sheep that lambed in an airspace separate from the flock had 11.3 times (95% CI: 2.9-43.6) the odds of seropositivity relative to other sheep. The practice of loaning sheep that returned to the farm increased odds of seropositivity by 8.1 times (95% CI: 1.8-33.6). Lambing pen hygiene practices also influenced odds of seropositivity. Relative to sheep from farms where all lambing pen hygiene measures were practiced after lambing (i.e., adding bedding, removing birth materials and disinfection), sheep from farms that only added bedding, or those that just added bedding and removed birthing materials had 5.9 times (95% CI: 1.1-32.1) and 9.0 times (95% CI: 2.2-36.9) the odds of seropositivity, respectively. These results can be used to inform prevention and control strategies with the aim of reducing C. burnetii exposure in sheep.

Coxiella burnetii seropositivity and associated risk factors in goats in Ontario, Canada.

Coxiella burnetii is a zoonotic bacterium, and infection in goats with this bacterium can result in abortion, stillbirth or birth of non-viable kids. A cross-sectional study was conducted to identify the seroprevalence and risk factors for C. burnetii exposure in Ontario goats. Sera were collected between August 2010 and February 2012, and tested for C. burnetii specific antibodies using an enzyme-linked immunosorbent assay (IDEXX). Overall, 63.2% (48/76, 95% CI=51.9-73.4) of farms had one or more seropositive goats. A higher farm-level seroprevalence of 78.6% (33/42) was found on dairy goat farms, compared to 44.1% (15/34) on meat goat farms (p<0.01). At the overall individual-animal level, 32.5% (714/2195, 95% CI=30.6-34.5) of goats were seropositive. Similarly, a higher individual-level seroprevalence was identified for dairy goats (43.7%, 633/1447) compared to meat goats (10.8%, 81/748) (p<0.001). A mixed multivariable logistic model that controlled for farm-level clustering identified risk factors associated with seropositivity (p<0.05). Increases in the female herd size (logarithmic scale) were associated with increased odds of seropositivity, while increases in male herd size had a negative association with seropositivity. If other sheep or goat farms were located in a 5-km radius, goats had 5.6 times (95% CI=1.01-30.8) times the odds of seropositivity compared to those that were not. Relative to goats from farms where all kidding pen hygiene was practiced (adding bedding, removing birth materials and disinfection after kidding), goats from farms which only added bedding and removed birth materials had a higher odds of seropositivity (OR=19.3, 95% CI=1.1-330.4), as did goats from farms which practiced none of these measures (OR=161.0, 95% CI=2.4-10822.2). An interaction term revealed kidding outdoors when there were no swine on farm had a protective effect on seropositivity compared to kidding indoors, or kidding outdoors with swine on the farm. These results can inform strategies to mitigate exposure to C. burnetii in Ontario.

Evaluating the effect of Focus Farms on Ontario dairy producers' knowledge, attitudes, and behavior toward control of Johne's disease.

This study evaluated a participatory-based, experiential learning program, Ontario Focus Farms (FF), which aimed to change dairy producer behavior to control Johne's disease (JD) in Ontario, Canada. The goals were to (1) assess the effect of FF on participating dairy producers' knowledge, attitudes, and behavior with regard to JD control; (2) compare changes in these factors among FF participants to changes among a group of nonparticipating dairy producers; and (3) describe the characteristics of producers who made at least one on-farm management change. Pre- and post-FF intervention questionnaires collected data on respondents' knowledge, attitudes, behavior, herd production, and demographic information; before and after JD-risk assessments were used to assess respondents' on-farm risk of JD transmission. Overall, 176 dairy producers participated in the FF process; 39.8% (70/176) of FF and 14.6% (52/357) of control participants responded to both the pre- and postintervention questionnaires. Upon comparison, FF respondents were more likely to be younger, have larger herds, and have higher management scores. The proportion of FF participants who reported making at least one on-farm change (81%) was significantly higher than that of control respondents (38%). Overall, FF respondents significantly changed their risk score in 4 out of 5 risk areas and had an average reduction of 13 points in their overall risk score between before and after risk assessments. Control respondents' risk assessment scores did not significantly change during the study period. In a JD knowledge assessment, FF and control respondents exhibited a moderate knowledge score before the intervention period, with median scores of 75.9% (22/29) in each group. The FF respondents significantly increased their score at the postintervention assessment, with a median of 82.8% (24/29); control-respondent scores did not significantly change. Both FF and control respondents held strong positive attitudes toward JD control and felt a moderate amount of social pressure from veterinarians and industry organizations to make on-farm changes. However, they questioned their ability to effectively control JD on the farm. Last, participating in FF, having a moderate herd management score, having a positive perception about the practicality of on-farm recommendations, and having a singular learning preference were associated with increased odds of making an on-farm change. Overall, the FF process appears to be effective at influencing producer behavior toward implementing on-farm management practices for JD control. Future JD control programs should consider implementing peer-learning extension processes, such as FF, in combination with other extension approaches, to influence producer behavior.

Clinical practice guidelines for the medical management of nonhospitalized ulcerative colitis: the Toronto consensus

BACKGROUND & AIMS:: The medical management of ulcerative colitis (UC) has improved through the development of new therapies and novel approaches that optimize existing drugs. Previous Canadian consensus guidelines addressed the management of severe UC in the hospitalized patient. We now present consensus guidelines for the treatment of ambulatory patients with mild to severe active UC. METHODS: A systematic literature search identified studies on the management of UC. The quality of evidence and strength of recommendations were rated according to the Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach. Statements were developed through an iterative online platform and then finalized and voted on by a working group of specialists. RESULTS: The participants concluded that the goal of therapy is complete remission, defined as both symptomatic and endoscopic remission without corticosteroid therapy. The consensus includes 34 statements focused on 5 main drug classes: 5-aminosalicylate (5-ASA), corticosteroids, immunosuppressants, anti-tumor necrosis factor (TNF) therapies, and other therapies. Oral and rectal 5-ASA are recommended first-line therapy for mild to moderate UC, with corticosteroid therapy for those who fail to achieve remission. Patients with moderate to severe UC should undergo a course of oral corticosteroid therapy, with transition to 5-ASA, thiopurine, anti-TNF (with or without thiopurine or methotrexate), or vedolizumab maintenance therapy in those who successfully achieve symptomatic remission. For patients with corticosteroid-resistant/dependent UC, anti-TNF or vedolizumab therapy is recommended. Timely assessments of response and remission are critical to ensuring optimal outcomes. CONCLUSIONS: Optimal management of UC requires careful patient assessment, evidence-based use of existing therapies, and thorough assessment to define treatment success.(AU)

Comparison of calculation methods used for the determination of anthelmintic resistance in sheep in a temperate continental climate.

This study compared results obtained with five different fecal egg count reduction (FECR) calculation methods for defining resistance to ivermectin, fenbendazole, and levamisole in gastrointestinal nematodes of sheep in a temperate continental climate: FECR1 and FECR2 used pre-and posttreatment fecal egg count (FEC) means from both treated and control animals, but FECR1 used arithmetic means, whereas FECR2 used geometric means; FECR3 used arithmetic means for pre- and posttreatment FECs from treated animals only; FECR4 was calculated using only arithmetic means for posttreatment FECs from treated and control animals; and FECR5 was calculated using mean FEC estimates from a general linear mixed model. The classification of farm anthelmintic resistance (AR) status varied, depending on which FECR calculation method was used and whether a bias correction term (BCT, i.e., half the minimum detection limit) was added to the zeroes or not. Overall, agreement between all methods was higher when a BCT was used, particularly when levels of resistance were low. FECR4 showed the highest agreement with all the other FECR methods. We therefore recommend that small ruminant clinicians use the FECR4 formula with a BCT for AR determination, as this would reduce the cost of the FECRT, while still minimizing bias and allowing for comparisons between different farms. For researchers, we recommend the use of FECR1 or FECR2, as the inclusion of both pre- and posttreatment FECs and use of randomly allocated animals in treatment and control groups makes these methods mathematically more likely to estimate the true anthelmintic efficacy.