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Objective: To create complexity groups based upon a patient's cardiac medical history and to test for group differences in health-related quality of life (HRQOL)., Methods: Patients 8-18 years with congenital heart disease (CHD) and parent-proxies from the Pediatric Cardiac Quality of Life Inventory (PCQLI) Testing Study were included. Outcome variables included PCQLI Total, Disease Impact, and Psychosocial Impact scores. Using a patient's medical history (cardiac, neurologic, psychological, and cognitive diagnosis), latent class analysis (LCA) was used to create CHD complexity groups. Covariates included demographics and burden of illness (number of: school weeks missed, physician visits in the past year, and daily medications). Generalized estimation equations tested for differences in burden of illness and patient and parent-proxy PCQLI scores., Results: Using 1482 CHD patients (60% male; 84% white; age 12.3 ± 3.0 years), latent class analysis (LCA) estimates showed 4 distinct CHD complexity groups (Mild, Moderate 1, Moderate 2, and Severe). Increasing CHD complexity was associated with increased risk of learning disorders, seizures, mental health problems, and history of stroke. Greater CHD complexity was associated with greater burden of illness (P < .01) and lower patient- and parent-reported PCQLI scores (P < .001)., Conclusions: LCA identified 4 congenital heart disease (CHD) complexity groupings. Increasing CHD complexity was associated with higher burden of illness and worse patient- and parent-reported HRQOL., Competing Interests: Declaration of Competing Interest Dr Marino is the creator of the PCQLI. The PCQLI is available for both clinical and research utilization for free. There are no other conflicts of interest to disclose. This research was funded by the following: NICHD K23 Grant (5-K23-HD048637-05), American Heart Association Grant (0465467), CHOP Institutional Development Fund, and CCHMC Research Foundation (31-554000-355514). The funders had no role in the design or conduct of the study., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Planning the design of a new trial comparing two treatments already in a network of trials with an a-priori plan to estimate the effect size using a network meta-analysis increases power or reduces the sample size requirements. However, when the comparison of interest is between a treatment already in the existing network (old treatment) and a treatment that hasn't been studied previously (new treatment), the impact of leveraging information from the existing network to inform trial design has not been extensively investigated. We aim to identify the most powerful trial design for a comparison of interest between an old treatment A and a new treatment Z, given a fixed total sample size. We consider three possible designs: a two-arm trial between A and Z ('direct two-arm'), a two-arm trial between another old treatment B and Z ('indirect two-arm'), and a three-arm trial among A, B, and Z., Methods: We compare the standard error of the estimated effect size between treatments A and Z for each of the three trial designs using formulas. For continuous outcomes, the direct two-arm trial always has the largest power, while for a binary outcome, the minimum variances among the three trial designs are conclusive only when [Formula: see text]. Simulation studies are conducted to demonstrate the potential for the indirect two-arm and three-arm trials to outperform the direct two-arm trial in terms of power under the condition of [Formula: see text]., Results: Based on the simulation results, we observe that the indirect two-arm and three-arm trials have the potential to be more powerful than a direct two-arm trial only when [Formula: see text]. This power advantage is influenced by various factors, including the risk of the three treatments, the total sample size, and the standard error of the estimated effect size from the existing network meta-analysis., Conclusions: The standard two-arm trial design between two treatments in the comparison of interest may not always be the most powerful design. Utilizing information from the existing network meta-analysis, incorporating an additional old treatment into the trial design through an indirect two-arm trial or a three-arm trial can increase power., (© 2023. The Author(s).)

The present study explored implicit and explicit honesty perceptions of White and Black children and whether these perceptions predicted legal decisions in a child abuse case. Participants consisted of 186 younger and 189 older adults from the online Prolific participant pool. Implicit racial bias was measured via a modified Implicit Association Test and explicit perceptions through self-reports. Participants read a simulated legal case where either a Black or White child alleged physical abuse against their sports coach, and they rated the honesty of the child's testimony and rendered a verdict. Participants were implicitly biased to associate honesty with White children over Black children, and this bias was stronger among older adults. In the legal vignette, for participants who read about a Black child victim, greater implicit racial bias predicted less trust in the child's testimony and a lower likelihood of convicting the coach of abusing the child. In contrast to their implicit bias, participants self-reported Black children as being more honest than White children, suggesting a divergence in racial attitudes across implicit and explicit measures. Implications for child abuse victims are discussed.

Objectives: To determine incidence of death in residential care facilities for people with disability in Ireland, primary cause of death, associations of facility characteristics and deaths, and to compare characteristics of deaths reported as expected and unexpected., Design: Descriptive cross-sectional study., Setting: All residential care facilities for people with disability operational in Ireland in 2019 and 2020 (n=1356)., Participants: n=9483 beds., Main Outcome Measures: All expected and unexpected deaths notified to the social services regulator. Cause of death as reported by the facility., Results: 395 death notifications were received in 2019 (n=189) and 2020 (n=206). 45% (n=178) were for unexpected deaths. Incidence of death per 1000 beds per year was 20.83 for all, 11.44 for expected and 9.39 for unexpected deaths. Respiratory disease was the most common cause of death, accounting for 38% (n=151) of all deaths. In adjusted negative binomial regression analysis, congregated settings versus non-congregated (incidence rate ratio (95% CI): 2.59 (1.80 to 3.73)) and higher bed numbers (highest vs lowest quartile) (4.02 (2.19 to 7.40)) were positively associated with mortality. There was also a positive n-shaped association with category of nursing staff-to-resident ratio when compared with zero nurses. Emergency services were contacted for 6% of expected deaths. Of the deaths reported as unexpected, 29% were receiving palliative care and 10.8% had a terminal illness., Conclusion: Although incidence of death was low, residents of congregated and larger settings had higher incidence of death than residents of other settings. This should be a consideration for practice and policy. Given the high contribution of respiratory diseases to deaths and the potential avoidability of these, there is a need for improved respiratory health management in this population. Nearly half of all deaths were reported as unexpected; however, overlap in the characteristics of expected and unexpected deaths highlights the need for clearer definitions., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: To achieve higher power or increased precision for a new trial, methods based on updating network meta-analysis (NMA) have been proposed by researchers. However, this approach could potentially lead to misinterpreted results and misstated conclusions. This work aims to investigate the potential inflation of type I error risk when a new trial is conducted only when, based on a p -value of the comparison in the existing network, a "promising" difference between two treatments is noticed. Methods: We use simulations to evaluate the scenarios of interest. In particular, a new trial is to be conducted independently or depending on the results from previous NMA in various scenarios. Three analysis methods are applied to each simulation scenario: with the existing network, sequential analysis and without the existing network. Results: For the scenario that the new trial will be conducted only when a promising finding ( p -value < 5 % ) is indicated by the existing network, the type I error risk increased dramatically (38.5% in our example data) when analyzed with the existing network and sequential analysis. The type I error is controlled at 5% when analyzing the new trial without the existing network. Conclusion: If the intention is to combine a trial result with an existing network of evidence, or if it is expected that the trial will eventually be included in a network meta-analysis, then the decision that a new trial is performed should not depend on a statistically "promising" finding indicated by the existing network., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ye, Wang and O’Connor.)

Background: In network meta-analysis, estimation of a comparative effect can be performed for treatments that are connected either directly or indirectly. However, disconnected trial networks may arise, which poses a challenge to comparing all available treatments of interest. Several modeling approaches attempt to compare treatments from disconnected networks but not without strong assumptions and limitations. Conducting a new trial to connect a disconnected network can enable calculation of all treatment comparisons and help researchers maximize the value of the existing networks. Here, we develop an approach to finding the best connecting trial given a specific comparison of interest., Methods: We present formulas to quantify the variation in the estimation of a particular comparative effect of interest for any possible connecting two-arm trial. We propose a procedure to identify the optimal connecting trial that minimizes this variation in effect estimation., Results: We show that connecting two treatments indirectly might be preferred to direct connection through a new trial, by leveraging information from the existing disconnected networks. Using a real network of studies on the use of vaccines in the treatment of bovine respiratory disease (BRD), we illustrate a procedure to identify the best connecting trial and confirm our findings via simulation., Conclusion: Researchers wishing to conduct a connecting two-arm study can use the procedure provided here to identify the best connecting trial. The choice of trial that minimizes the variance of a comparison of interest is network dependent and it is possible that connecting treatments indirectly may be preferred to direct connection., (© 2023. The Author(s).)

Background: Reporting of clinical trials conducted in client- and shelter-owned dog and cat populations is not optimal, which inhibits the ability to assess the reliability and validity of trial findings and precludes the ability to include some trials in evidence synthesis., Objective: To develop a reporting guideline for parallel group and crossover trials that addresses the unique features and reporting requirements for trials conducted in client- and shelter-owned dog and cat populations., Design: Consensus statement., Setting: Virtual., Participants: Fifty-six experts from North America, the United Kingdom, Europe, and Australia working in academia, government (research and regulatory agencies), industry, and clinical veterinary practice., Methods: A steering committee created a draft checklist for reporting criteria based upon the CONSORT statement and the CONSORT extensions for reporting of abstracts and crossover trials. Each item was presented to the expert participants and was modified and presented again until >85% of participants were in agreement about the inclusion and wording of each item in the checklist., Results: The final PetSORT checklist consists of 25 main items with several sub-items. Most items were modifications of items contained in the CONSORT 2010 checklist or the CONSORT extension for crossover trials, but 1 sub-item pertaining to euthanasia was created de novo ., Conclusion: The methods and processes used to develop this guideline represent a novel departure from those used to create other reporting guidelines, by using a virtual format. The use of the PetSORT statement should improve reporting of trials conducted in client- and shelter-owned dogs and cats and published in the veterinary research literature., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ruple, Sargeant, Selmic and O'Connor.)

Well-designed randomized controlled trials (RCTs) provide the best evidence of the primary research designs for evaluating the effectiveness of interventions. However, if RCTs are incompletely reported, the methodological rigor with which they were conducted cannot be reliably evaluated and it may not be possible to replicate the intervention. Missing information also may limit the reader's ability to evaluate the external validity of a trial. Reporting guidelines are available for clinical trials in human healthcare (CONSORT), livestock populations (REFLECT), and preclinical experimental research involving animals (ARRIVE 2.0). The PetSORT guidelines complement these existing guidelines, providing recommendations for reporting controlled trials in pet dogs and cats. The rationale and scientific background are explained for each of the 25 items in the PetSORT reporting recommendations checklist, with examples from well-reported trials., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Sargeant, Ruple, Selmic and O'Connor.)

Background: A critical step in trial design is determining the sample size and sample allocation to ensure the proposed study has sufficient power to test the hypothesis of interest: superiority, equivalence, or non-inferiority. When data are available from prior trials and leveraged with the new trial to answer the scientific questions, the value of society's investment in prior research is increased. When prior information is available, the trial design including the sample size and allocation should be adapted accordingly, yet the current approach to trial design does not utilize such information. Ensuring we maximize the value of prior research is essential as there are always constraints on resources, either physical or financial, and designing a trial with adequate power can be a challenge., Methods: We propose an approach to increasing the power of a new trial by incorporating evidence from a network meta-analysis into the new trial design and analysis. We illustrate the methodology through an example network meta-analysis, where the goal is to identify the optimal allocation ratio for the new three-arm trial, which involves the reference treatment, the new treatment, and the negative control. The primary goal of the new trial is to show that the new treatment is non-inferior to the reference treatment. It may also be of interest to know if the new treatment is superior to the negative control. We propose an optimal treatment allocation strategy which is derived from minimizing the standard error of the log odds ratio estimate of the comparison of interest. We conducted a simulation study to assess the proposed methods to design a new trial while borrowing information from the existing network meta-analysis and compare it to even allocation methods., Results: Using mathematical derivation and simulations, we document that our proposed approach can borrow information from a network meta-analysis to modify the treatment allocation ratio and increase the power of the new trial given a fixed total sample size or to reduce the total sample size needed to reach a desired power., Conclusions: When prior evidence about the hypotheses of interest is available, the traditional equal allocation strategy is not the most powerful approach anymore. Our proposed methodology can improve the power of trial design, reduce the cost of trials, and maximize the utility of prior investments in research., (© 2022. The Author(s).)

Clinical trials are a valuable study design for evaluating interventions when it is ethical and feasible for investigators to randomly allocate study animals to intervention groups. Researchers may choose to evaluate the comparative efficacy of intervention groups for their effect on outcomes that are relevant to the specific objectives of their trial. However, the results across multiple trials on the same intervention and with the same outcome should be considered when making decisions on whether to use an intervention, because the results of a single trial are subject to sampling error and do not reflect all biological variability. The objective of this review was to provide an overview of important concepts when selecting intervention groups and outcomes within a randomized controlled trial, and when building a body of evidence for intervention efficacy across multiple trials. Empirical evidence is presented to highlight that integrating and interpreting the efficacy of an intervention across trials is hindered by a lack of replication of interventions across trials. Inconsistency in the outcomes and their measurement among trials also limits the ability to build a body of evidence for the efficacy of interventions. The development of core outcome sets for specific topic areas in dairy science, updated as necessary, may improve consistency across trials and aid in the development of a body of evidence for evidence-based decision-making., (The Authors. Published by Elsevier Inc. and Fass Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Observational research may be conducted to predict an outcome or to identify associations between an intervention or risk factor (an "exposure") and an outcome. However, the end goal of observational research often is to identify exposures that can be manipulated to improve an outcome, meaning that the aim is identify causal relationships. Causal inference from observational studies may be appropriate when an exposure-outcome of interest is identified, causal reasoning is used to identify confounders, confounders are adequately controlled, and theoretical issues, such as temporality, are considered. If these conditions are not met, causal inference cannot be made in an observational study. The objective of our study was to explore the use of causal language in veterinary observational studies, and to compare the use of causal language between studies that appear to be predictive or associational in purpose vs. those that appear to be exploring causal relationships. The dataset comprised 200 observational studies in veterinary species published between 2020 and 2022. The majority (117 out of 200) were cross-sectional studies. There were 48 studies that described an exposure-outcome of interest, and we considered these studies to be exploring potential causal relationships; of note, this liberal categorization would be anticipated to overestimate the proportion of studies suitably designed for causal inference. Overall, 172 studies (86%) used causal wording in at least one section of the article. Causal language was used in 128/152 (84%) of studies exploring predictions or associations; this language implies causation when it is not appropriate to do so. In studies designed such that causal inference might be possible, 44/48 (92%) used causal language in one or more sections. There were no substantive differences in the use of causal wording between observational study designs, exposure types, or whether the first author's affiliation was a country in which English is an official language. There is a need for authors of veterinary observational studies to explicitly state the purpose of the study (associational, predictive, or causal), and to use causal wording appropriately based on the aim of the study., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sargeant, O'Connor, Totton and Vriezen.)

Research has explored age-related and cultural differences in moral evaluations of dishonesty; however, this has not yet been examined in an aging context. The present study provided a novel account of how younger and older adults (in Canada, Singapore, and China; N  = 401) morally evaluate adults' truths and lies in antisocial, modesty, and politeness settings. Participants completed a questionnaire assessing how acceptable it is for adults to tell the truth or a lie in given social scenarios, and they reported on their levels of collectivism and individualism. In all countries, older adults provided more favorable evaluations to blunt and immodest truths than younger adults did. Compared with younger adults, older adults provided harsher evaluations to Polite Lies (in Canada and China) and Modesty Lies (in Canada and Singapore). Thus, there may be an age-related increase in the acceptability of direct honesty over good-intentioned lies, and this age effect is somewhat stable across cultures. Older adults were also more lenient in evaluations of an antisocial lie to conceal an affair compared to younger adults . Overall, adults in China tended to rate lies less negatively, and their greater levels of collectivism mediated their greater approval of polite lies. The present results demonstrate that evaluations of (dis)honesty differ as a function of age and culture and these results can assist in developing a more complete lifespan model of the morality of dishonesty., Supplementary Information: The online version contains supplementary material available at 10.1007/s12144-022-03785-6., Competing Interests: Conflict of interestThe authors have no conflict of interest to report., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022, Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Clinical decisions in human and veterinary medicine should be based on the best available evidence. The results of primary research are an important component of that evidence base. Regardless of whether assessing studies for clinical case management, developing clinical practice guidelines, or performing systematic reviews, evidence from primary research should be evaluated for internal validity i.e., whether the results are free from bias (reflect the truth). Three broad approaches to evaluating internal validity are available: evaluating the potential for bias in a body of literature based on the study designs employed (levels of evidence), evaluating whether key study design features associated with the potential for bias were employed (quality assessment), and applying a judgement as to whether design elements of a study were likely to result in biased results given the specific context of the study (risk of bias assessment). The level of evidence framework for assessing internal validity assumes that internal validity can be determined based on the study design alone, and thus makes the strongest assumptions. Risk of bias assessments involve an evaluation of the potential for bias in the context of a specific study, and thus involve the least assumptions about internal validity. Quality assessment sits somewhere between the assumptions of these two. Because risk of bias assessment involves the least assumptions, this approach should be used to assess internal validity where possible. However, risk of bias instruments are not available for all study designs, some clinical questions may be addressed using multiple study designs, and some instruments that include an evaluation of internal validity also include additional components (e.g., evaluation of comprehensiveness of reporting, assessments of feasibility or an evaluation of external validity). Therefore, it may be necessary to embed questions related to risk of bias within existing quality assessment instruments. In this article, we overview the approaches to evaluating internal validity, highlight the current complexities, and propose ideas for approaching assessments of internal validity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sargeant, Brennan and O'Connor.)

Research allows for the discovery of new knowledge and is integral to evidence-based decision-making. However, research is only useful if it is available. The aim of this study was to explore publication and accessibility of full-text reports for controlled trials (experimental studies) conducted in dairy cattle. We determined the proportion of controlled trials presented as abstracts at the 2015 Joint Annual Meeting of the American Dairy Science Association and the American Society of Animal Science or the 2015 American Association of Bovine Practitioners Annual Conference that were subsequently published. Factors associated with publication or non-publication in a peer-reviewed journal were evaluated using risk ratios. For trials that were subsequently published, we compared the sample size, numerical results, and inference between the conference abstract and the subsequent publication. Approximately half of the trials (177 out of 380) reported at conferences were subsequently published. Source conference, whether the conference abstract results were described as preliminary, whether there was at least one positive outcome, author affiliation, whether the trial involved deliberate disease induction, and total sample size were not strongly associated with subsequent publication. For trials that were published, the sample size differed between the conference proceedings and full publications for 22%, the numerical results differed in 29%, and the inference differed for 11%. We also evaluated whether trials included in 9 recent systematic reviews were in English and were available without subscription or cost. Of the 390 trials included in recent systematic reviews, approximately 40% were available only through subscription or access fee. These results suggest that publication and accessibility of research results is suboptimal, representing an area of wastage in dairy cattle research. Researchers should ensure that they publish the results of trials comprehensively in searchable publications, even if the results are not novel or do not detect expected differences, and, when possible, make the results available freely., (The Authors. Published by Elsevier Inc. and Fass Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Objective: To evaluate the use of mesenchymal stem cells (MSCs), autologous conditioned serum (ACS), platelet-rich plasma (PRP), and autologous protein solution (APS) for the treatment of equine musculoskeletal disease by diplomates of the American College of Veterinary Surgery (ACVS), and American College of Veterinary Sports Medicine and Rehabilitation (ACVSMR)., Study Design: Cross-sectional study., Sample Population: Diplomates (n = 423)., Methods: An email link was sent to ACVS and ACVMR diplomates. A survey contained 59 questions regarding demographics, as well as indications, frequency, adverse effects, and limitations of use. Responses were analyzed using Fisher's exact test., Results: One hundred and fifty four surveys were analyzed. Years in practice and type of practice were not associated with biologic therapy use. PRP was the most used therapy (120/137; 87.5%). PRP and MSCs were most often administered intralesionally while ACS and APS were most often administered intra-articularly. ACS (50/104; 48.1%) treatment was repeated commonly within 2 weeks of initial injection. MSCs (39/90; 43.3%) and PRP (38/100; 38%) were commonly repeated 1-2 months after initial injection and APS was typically repeated >4 months after initial injection (21/53; 39.6%). Local inflammation and expense were the most common adverse effect and limitation of use., Conclusion: Diplomates most commonly utilized PRP and MSC intralesionally for soft-tissue injuries, and ACS and ACP intra-articularly for joint injury. Protocols for repeated administration varied widely. Local inflammation was a clinical concern with the use of biologics., Clinical Significance: Biologic therapies are used commonly by ACVS and ACVSMR diplomates for soft tissue and joint disease., (© 2022 The Authors. Veterinary Surgery published by Wiley Periodicals LLC on behalf of American College of Veterinary Surgeons.)

The role of processing bodies (P-bodies), key sites of post-transcriptional control, in adult stem cells remains poorly understood. Here, we report that adult Drosophila intestinal stem cells, but not surrounding differentiated cells such as absorptive enterocytes (ECs), harbor P-bodies that contain Drosophila orthologs of mammalian P-body components DDX6, EDC3, EDC4, and LSM14A/B. A targeted RNAi screen in intestinal progenitor cells identified 39 previously known and 64 novel P-body regulators, including Patr-1, a gene necessary for P-body assembly. Loss of Patr-1-dependent P-bodies leads to a loss of stem cells that is associated with inappropriate expression of EC-fate gene nubbin. Transcriptomic analysis of progenitor cells identifies a cadre of such weakly transcribed pro-differentiation transcripts that are elevated after P-body loss. Altogether, this study identifies a P-body-dependent repression activity that coordinates with known transcriptional repression programs to maintain a population of in vivo stem cells in a state primed for differentiation., Competing Interests: Declaration of interests The authors declare no competing interests., (Published by Elsevier Inc.)

Despite a recent wave in global recognition of the rights of transgender and gender-diverse populations, referred to in this text by the umbrella label of trans*, international law continues to presume a cisgender binary definition of gender - dismissing the lived realities of trans* individuals throughout the world. This gap in international legal recognition and protection has fundamental implications for health, where trans* persons have been and continue to be subjected to widespread discrimination in health care, longstanding neglect of health needs, and significant violations of bodily autonomy.

Honest disclosures of COVID-19 behaviors and symptoms is critical. A sample of adults on MTurk ( N =  451, 20-82 years of age) were asked if they have concealed social distancing practices, COVID-19 symptoms, and quarantine instructions, as well as how they evaluated others' COVID-19 concealment. Those who believed they had contracted COVID-19 engaged in greater rates of concealment and evaluated concealment more positively compared to those without the virus. As age and communal orientation increased, COVID-19 concealment behaviors decreased, and evaluations of this concealment were rated more negatively. Implications for public health initiatives and psychological theory on concealing health information is discussed.

Salmonella contamination of livestock feed is a serious veterinary and public health issue. In this study we used a systematic review to assess the prevalence and characterization of Salmonella isolates detected in raw feed components, feed milling equipment and finished feed from 97 studies published from 1955 to 2020 across seven global regions. Eighty-five studies were included in a meta-analyses to estimate the combined prevalence of Salmonella detection and to compare the risk of contamination associated with different sample types. We found the overall combined prevalence estimate of Salmonella detection was 0.14 with a prevalence of 0.18 in raw feed components, 0.09 in finished feed and 0.08 in feed milling equipment. Animal based raw feed components were 3.9 times more likely to be contaminated with Salmonella than plant based raw feed components. Differences between studies accounted for 99 % of the variance in the prevalence estimate for all sample types and there was no effect of region on the prevalence estimates. The combined prevalence of Salmonella detection in raw feed components decreased from 0.25 in 1955 to 0.11 in 2019. The proportion of Salmonella isolates that were resistant to antimicrobials was largest for amikacin (0.20), tetracycline (0.18) streptomycin (0.17), cefotaxime (0.14) and sulfisoxazole (0.11). The prevalence of Salmonella contamination of animal feed varies widely between individual studies and is an ongoing challenge for the commercial feed industry. Control relies on the vigilant monitoring and control of Salmonella in each individual mill., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Network meta-analysis (NMA) is a statistical method used to combine results from several clinical trials and simultaneously compare multiple treatments using direct and indirect evidence. Statistical heterogeneity is a characteristic describing the variability in the intervention effects being evaluated in the different studies in network meta-analysis. One approach to dealing with statistical heterogeneity is to perform a random effects network meta-analysis that incorporates a between-study variance into the statistical model. A common assumption in the random effects model for network meta-analysis is the homogeneity of between-study variance across all interventions. However, there are applications of NMA where the single between-study assumption is potentially incorrect and instead the model should incorporate more than one between-study variances., Methods: In this paper, we develop an approach to testing the homogeneity of between-study variance assumption based on a likelihood ratio test. A simulation study was conducted to assess the type I error and power of the proposed test. This method is then applied to a network meta-analysis of antibiotic treatments for Bovine respiratory disease (BRD)., Results: The type I error rate was well controlled in the Monte Carlo simulation. We found statistical evidence (p value = 0.052) against the homogeneous between-study variance assumption in the network meta-analysis BRD. The point estimate and confidence interval of relative effect sizes are strongly influenced by this assumption., Conclusions: Since homogeneous between-study variance assumption is a strong assumption, it is crucial to test the validity of this assumption before conducting a network meta-analysis. Here we propose and validate a method for testing this single between-study variance assumption which is widely used for many NMA., (© 2021. The Author(s).)

Cyclosporiasis is a global, emerging disease in humans caused by Cyclospora cayetanensis. The role of animals in the epidemiology of cyclosporiasis is not fully understood. We conducted a narrative review of the published literature on C. cayetanensis in animals. MEDLINE ® (Web of Science ™ ), Agricola (ProQuest), CABI Global Health (1979 to December 2020) and Food Science and Technology Abstracts (EBSCOhost) (1979 to February 2020) were searched. Studies of C. cayetanensis in or on any species of animal were eligible. Thirteen relevant studies were found. C. cayetanensis was found in wild and farmed Mediterranean mussels (Mytilus galloprovincialis), wild grooved carpet shell clams (Ruditapes decussatus) and in the faeces of dogs (domestic and street), wild chickens, wild rhesus macaques (Macaca mulatta), chimpanzees (Pan troglodytes) from a wildlife research centre, and Cynomolgus monkeys (Macaca fascicularis) from an experimental primate research centre. As the small intestines of the naturally exposed animals were not biopsied, existence of a natural animal reservoir of C. cayetanensis could not be confirmed. Animals shedding oocysts in their faeces may be paratenic hosts. Investigators were able to successfully infect the following animals with C. cayetanensis: oysters, Asian freshwater clams (Corbicula fluminea), Swiss albino mice and guinea pigs. Future non-laboratory studies of animals should use PCR coupled with DNA sequencing to confirm that the species found is C. cayetanensis. The potential role of animals in the transport of oocysts and contamination of food, water, and soil could be explored through future primary research., (© 2021 Wiley-VCH GmbH.)

Systematic reviews are a valuable tool for evaluating the efficacy of interventions and for quantifying associations. To be properly assessed, reviews must be comprehensively reported. The primary objective of this study was to evaluate the completeness of reporting of systematic reviews and meta-analyses in animal health. The secondary objective was to further characterize methods for literature searches and risk of bias assessments and to document whether the risk of bias component represented an assessment of risk of bias, study quality, or levels of evidence based on the primary studies included. The dataset comprised 91 systematic reviews or meta-analyses of interventions or exposures with at least one health outcome measured at the animal or animal byproduct level, in any companion or food animal species and published between 2014 and 2018. Two reviewers independently collected information on whether each item in the PRISMA reporting guidelines was reported, with disagreements resolved by consensus. There was considerable variability in the completeness of reporting among reviews; some items, such as eligibility criteria for inclusion, were reported in most reviews (>65 %). Other items were not consistently reported; for instance, in 60 % (54) of the reviews there was no information provided on the sample size of individual studies, populations, interventions and comparators, outcomes, or follow up period. Although 89 % (81) of systematic reviews with meta-analysis included the effect size estimate and confidence intervals, it was not possible to determine which study designs were included for 30 % (14) of reviews. Results from individual PRISMA item questions were combined to determine whether all aspects of each recommended item were reported; 71 % of items were adequately reported in less than half the systematic reviews without a meta-analysis, 35 % of the items were adequately reported in less than half the systematic reviews with a meta-analysis, and 71 % of items were adequately reported in less than half of the meta-analyses without a systematic review component. An assessment of individual study level bias was included in 64 % of the reviews, although this component included an evaluation of risk of bias (35 reviews), study quality (25 reviews), or levels of evidence based on study design (12 reviews). Reporting guidelines or clinical guidelines were inappropriately used to assess risk of bias in 9 reviews. Overall, the results of this study reveal that reporting of systematic reviews in the animal health literature is suboptimal and improvements are needed to enhance utility of these reviews., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: The emergence of antimicrobial resistance across populations is a global threat to public health. Surveillance programs often monitor human and animal populations to evaluate trends of emergence in these populations. Many national level antibiotic resistance surveillance programs quantify the proportion of resistant bacteria as a means of monitoring emergence and control measures. The reason for monitoring these different populations are many, including interest in similar changes in resistance which might provide insight into emergence and control options., Methods: In this research, we developed a method to quantify the correlation in antimicrobial resistance across populations, for the conventionally unnoticed mean shift of the susceptible bacteria. With the proposed Bayesian latent class mixture model with censoring and multivariate normal hierarchy, we address several challenges associated with analyzing the minimum inhibitory concentration data., Results: Application of this approach to the surveillance data from National Antimicrobial Resistance Monitoring System led to a detection of positive correlation in the central tendency of azithromycin resistance of the susceptible populations from Salmonella serotype Typhimurium across food animal and human populations., Conclusions: Our proposed approach has been shown to be accurate and superior to the commonly used naïve estimation by simulation studies. Further implementation of this Bayesian model could serve as a useful tool to indicate the co-existence of antimicrobial resistance, and potentially a need of clinical intervention., (© 2021. The Author(s).)

Antimicrobial resistance (AMR) developed by Salmonella within animals used for food products is a major global issue. Monitoring AMR in animals destined for slaughter is, therefore, critical. Abattoirs may serve as potential candidate checkpoints for monitoring resistance patterns on farms. A complicating factor, however, is the impact of lairage on Salmonella detected in pigs at slaughter. This study sought to compare AMR patterns in Salmonella spp. in swine collected upon arrival (fecal samples) at the abattoir with those at postslaughter (cecal samples) and evaluate the feasibility of using slaughterhouse samples for surveillance of prevailing AMR Salmonella on farms. Eighty-four Salmonella isolates were recovered from a large, midwestern U.S. abattoir between September and November 2013. Isolates were tested for phenotypic AMR to 12 antimicrobials using the broth microdilution assay. Whole-genome sequencing identified the AMR genes harbored by the strains. Significant differences were observed in the isolate phenotypes and genotypes; however, no significant difference was observed in genotypic resistance patterns. Hence, the AMR profiles of Salmonella spp. postslaughter cannot be predicted from preslaughter samples. Further research considering the genetic diversity of isolates and statistical power of the genotypic analysis is warranted to improve the performance of WGS-inferred antimicrobial susceptibility.

The purpose of this article is to discuss the host as a cause of infectious bovine keratoconjunctivitis (IBK). The focus is on the host genetics rather than characteristics of the host, such as age, sex, and season of birth. From 4 conducted studies, estimates of IBK heritability are generally less than 0.15, except for some estimates for Herefords and Angus cattle around 0.2 and 1 study reporting a heritability of 0.33. These magnitudes of heritability are typically described as low to moderate. Quantitative trait locus on chromosome 1, 2, 12, 13, 20, and 21 has been associated with IBK resistance., Competing Interests: Disclosure The author has nothing to disclose., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Pili and cytotoxins are important virulence factors and antigens for Moraxella spp. Local and systemic immunity may play a role in the body's response to infectious bovine keratoconjunctivitis (IBK). No evidence exists that eliminating the carrier state for IBK is possible or beneficial. Evidence for efficacious transfer of passive immunity from dams to calves is conflicting. Autogenous vaccines and commercial vaccines for putative pathogens for IBK have not yet shown efficacy in blinded randomized field trials. Study design features, such as randomization, blinding, diagnostic criteria, and use of a placebo, reduce the risk of bias in vaccine studies for IBK., Competing Interests: Disclosure The authors have no commercial or financial conflicts of interest or funding sources to declare., (Copyright © 2021 Elsevier Inc. All rights reserved.)

In this article, the evidence base for treating infectious bovine keratoconjunctivitis (IBK) is discussed. First, we summarize the available evidence for antibiotic treatments registered in North America. We then discuss the evidence base for nonantibiotic alternatives. We do not discuss antibiotic treatments that do not use registered protocols; such information is available in another review. Finally, we discuss how the research community could generate more evidence for effective treatments and the comparative efficacy information to help veterinarians and producers decide between treatment options., Competing Interests: Disclosure Both the authors have nothing to disclose., (Copyright © 2021 Elsevier Inc. All rights reserved.)

In this article, the authors summarize the future needs from a research perspective to make the greatest gains. They discuss the areas of research: diagnosis, epidemiology, economic impact, prevention, and treatment. In some areas, simple studies with little cost could be conducted that would quickly add to the evidence base. In other areas, substantial investment is needed if new study approaches, which do not repeat past studies' failures, are to be conducted. To maximize the value of research funding, it is essential to critically evaluate the information gains from prior studies and ensure that studies increase knowledge incrementally., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Establishing causation, otherwise known as causal assessment, is a difficult task, made more difficult by the variety of causal assessment frameworks available to consider. In this article, Bradford Hill viewpoints are used to discuss the evidence base for Moraxella bovis and Moraxella bovoculi being component causes of infectious bovine keratoconjunctivitis. Each of the nine Bradford Hill viewpoints are introduced and explained: strength, consistency, specificity, temporality, biologic gradient, plausibility, coherence, experiment, and analogy. Examples of how the viewpoints have been applied for other causal relations are provided, and then the evidence base for M bovis and M bovoculi is discussed., (Copyright © 2021. Published by Elsevier Inc.)

Environmental factors that contribute to the pathogenesis of infectious bovine keratoconjunctivitis (IBK) include face flies, ultraviolet (UV) radiation, and mechanical irritation from plant awns or dust. Limited research has shown face fly control to be associated with lower incidence of IBK. UV radiation is known to cause corneal irritation and damage in mammalian species. The increased formation of corneal dark cells has been observed following UV radiation in exposed calves. Moraxella bovis preferentially binds to corneal dark cells where it can be found in pits, which may be formed due to bacterial contact. Little is known about the efficacy of management of pasture plants on the prevention of IBK., Competing Interests: Disclosure The authors have no commercial or financial conflicts of interest or funding sources to declare., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The present study assessed how accurate adults are at detecting fraudulent e-mail activity. A total of 100 younger (18-26 years) and 96 older adults (60-90 years) categorized a series of e-mails as legitimate or fraudulent phishing schemes and self-reported their fraud experiences. Younger and older adults did not differ in accuracy rates when categorizing the e-mails (72%), but older adults used a "high-suspicion" strategy where they were more likely to mislabel a legitimate e-mail as fraudulent compared to younger adults. Younger adults were less likely to be targeted by fraud than older adults, but the groups were victimized at similar rates. Being a prior fraud victim negatively related to e-mail detection performance, but this differed across age groups and the extent of fraud experience. Together, these results provide insight into the relation between fraud experience and the ability to detect e-mail scams and can inform fraud prevention and education initiatives.

There is mixed evidence on the impact of delay task difficulty on prospective memory (PM) performance and little research has examined this among older adults. The present study examined younger (N = 60) and older (N = 57) adults' prospective memory (PM) performance after completing an easy or difficult Raven's matrices task. To assess whether delay difficulty impacted how often participants thought about their PM intention, participants were asked to report on what they thought about during the delay task itself and retrospectively after all tasks were completed. Younger adults outperformed older adults on the PM task; however, delay task difficulty had no impact PM for either age group. Reports of thinking about the intention during the delay task differed by age group depending whether they were online or retrospective, however, overall greater reports of thinking about the intention was positively associated with PM performance.

To meet urgent decisional needs of retirement/nursing home residents and their families, our interdisciplinary stakeholder team rapidly developed and disseminated patient decision aids (PtDAs) regarding leaving one's residence during the COVID-19 pandemic. The development steps were as follows: identify urgent decisional needs, develop PtDAs using the Ottawa Decision Support Framework template and minimal International PtDA Standards, obtain stakeholder feedback, broadly disseminate, and incorporate user feedback. Within 2 wk, we developed 2 PtDAs for retirement and nursing home living environments that were informed by decisional needs (identified from public responses to related media reports), current pandemic regulations/guidance, and recent systematic reviews. Within 3 wk of their dissemination (websites, international PtDA inventory, Twitter, Facebook, media interviews), the PtDAs were downloaded 10,000 times, and user feedback was positive. Our expert team showed feasible rapid development and wide dissemination of PtDAs to respond to urgent decisional needs. Development efficiencies included access to a well-tested theory-based PtDA template, recent evidence syntheses, and values-based public responses to media reports. Future research includes methods for rapidly collecting user feedback, facilitating implementation, and measuring use and outcomes.

Cyclospora cayetanensis is a parasite causing cyclosporiasis (an illness in humans). Produce (fruits, vegetables, herbs), water and soil contaminated with C. cayetanensis have been implicated in human infection. The objective was to conduct a scoping review of primary research in English on the detection, epidemiology and control of C. cayetanensis with an emphasis on produce, water and soil. MEDLINE® (Web of ScienceTM), Agricola (ProQuest), CABI Global Health, and Food Science and Technology Abstracts (EBSCOhost) were searched from 1979 to February 2020. Of the 349 relevant primary research studies identified, there were 75 detection-method studies, 40 molecular characterisation studies, 38 studies of Cyclospora in the environment (33 prevalence studies, 10 studies of factors associated with environmental contamination), 246 human infection studies (212 prevalence/incidence studies, 32 outbreak studies, 60 studies of environmental factors associated with non-outbreak human infection) and eight control studies. There appears to be sufficient literature for a systematic review of prevalence and factors associated with human infection with C. cayetanensis. There is a dearth of publicly available detection-method studies in soil (n = 0) and water (n = 2), prevalence studies on soil (n = 1) and studies of the control of Cyclospora (particularly on produce prior to retail (n = 0)).

This work presents a rapid and reliable method to recover spermatozoa from Super Absorbent Polymers (SAPs) commonly found in sanitary protection products such as nappies and sanitary towels. The use of salt solutions was investigated and a protocol was developed using a calcium chloride (CaCl 2 ) solution to release semen deposited onto a selected SAP containing product. The method was tested on ultra-sanitary towel samples treated with a known amount of semen. A range of treatments were examined; some samples were prepared and immediately frozen for storage and others were allowed to air dry overnight to replicate the condition of similar items recovered for examination in sexual offence cases. The method allowed the collection of low yields of spermatozoa, but these were still sufficient for microscopic identification of intact heads and to obtain ESI17 DNA profiles from all the samples. This report presents the method, the results obtained and discusses prospective adaptations to the method for validation to implement the method into forensic casework., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The current study is the first to provide a comprehensive examination of the activation-decision-construction model (Walczyk, Roper, Seemann, & Humphrey, 2003, 2009) in relation to young children's lie-telling and lie maintenance. Young children (3 to 4 years of age, N = 93) completed the temptation-resistance paradigm to elicit a transgression (peeking at a forbidden toy). Children were asked if they peeked at the toy (initial lie) and what they thought the toy was (lie maintenance). A battery of executive functioning tasks was administered (working memory, inhibitory control, planning). With increased inhibitory control on a response inhibition task, children were significantly more likely to lie. With increased inhibitory control on a conflict inhibition task and superior planning on a planning task, children were significantly more likely to maintain their lies. Support for the activation-decision-construction model in relation to young children's deception is discussed. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Background . The Ottawa Decision Support Framework (ODSF) has been used for 20 years to assess and address people's decisional needs. The evidence regarding ODSF decisional needs has not been synthesized. Objectives . To synthesize evidence from ODSF-based decisional needs studies, identify new decisional needs, and validate current ODSF decisional needs. Methods . A mixed-studies systematic review. Nine electronic databases were searched. Inclusion criteria: studies of people's decisional needs when making health or social decisions for themselves, a child, or a mentally incapable person, as reported by themselves, families, or practitioners. Two independent authors screened eligibility, extracted data, and quality appraised studies using the Mixed Methods Appraisal Tool. Data were analyzed using narrative synthesis. Results . Of 4532 citations, 45 studies from 7 countries were eligible. People's needs for 101 unique decisions (85 health, 16 social) were reported by 2857 patient decision makers ( n = 36 studies), 92 parent decision makers ( n = 6), 81 family members ( n = 5), and 523 practitioners ( n = 21). Current ODSF decisional needs were reported in 2 to 40 studies. For 6 decisional needs, there were 11 new (manifestations): 1) information (overload, inadequacy regarding others' experiences with options), 2) difficult decisional roles (practitioner, family involvement, or deliberations), 3) unrealistic expectations (difficulty believing outcome probabilities apply to them), 4) personal needs (religion/spirituality), 5) difficult decision timing (unpredictable), and 6) unreceptive decisional stage (difficulty accepting condition/need for treatment, powerful emotions limiting information processing, lacking motivation to consider delayed/unpredictable decisions). Limitations . Possible publication bias (only peer-reviewed journals included). Possible missed needs (non-ODSF studies, patient decision aid development studies, 3 ODSF needs added in 2006). Conclusion . We validated current decisional needs, identified 11 new manifestations of 6 decisional needs, and recommended ODSF revisions.

The causal effect of an exposure on an outcome of interest in an observational study cannot be estimated directly if the confounding variables are not controlled. Many approaches are available for estimating the causal effect of an exposure. In this manuscript, we demonstrate the advantages associated with using inverse probability weighting (IPW) and doubly robust estimation of the odds ratio in terms of reduced bias. IPW approach can be used to adjust for confounding variables and provide unbiased estimates of the exposure's causal effect. For cluster-structured data, as is common in animal populations, inverse conditional probability weighting (ICPW) approach can provide a robust estimation of the causal effect. Doubly robust estimation can provide a robust method even when the specification of the model form is uncertain. In this paper, the usage of IPW, ICPW, and doubly robust approaches are illustrated with a subset of data with complete covariates from the Australian-based National Bovine Respiratory Disease Initiative as well as simulated data. We evaluate the causal effect of prior bovine viral diarrhea exposure on bovine respiratory disease in feedlot cattle. The results show that the IPW, ICPW and doubly robust approaches would provide a more accurate estimation of the exposure effect than the traditional outcome regression model, and doubly robust approaches are the most preferable overall., Competing Interests: The authors have declared that no competing interests exist.

Network meta-analysis is a general approach to integrate the results of multiple studies in which multiple treatments are compared, often in a pairwise manner. In this tutorial, we illustrate the procedures for conducting a network meta-analysis for binary outcomes data in the Bayesian framework using example data. Our goal is to describe the workflow of such an analysis and to explain how to generate informative results such as ranking plots and treatment risk posterior distribution plots. The R code used to conduct a network meta-analysis in the Bayesian setting is provided at GitHub., (Copyright © 2020 Hu, O'Connor, Wang, Sargeant and Winder.)

Background: Retention in opioid substitution (OST) treatment is associated with substantial reductions in all cause and overdose mortality. This systematic review aims to identify both protective factors supporting retention in OST, and risk factors for treatment dropout., Methods: A systematic search was performed using MEDLINE, Embase, PsycInfo, CINAHL and Web of Science (January 2001 to October 2019). Randomised controlled trials (RCTs) and observational cohort studies reporting on retention rates and factors associated with retention in OST were included. Factors associated with treatment retention and dropout were explored according to the Maudsley Addiction Profile. A narrative synthesis is provided., Results: 67 studies were included in this review (4 RCTs and 63 observational cohort studies; N = 294,592), all assessing factors associated with retention in OST or treatment dropout. The median retention rate across observational studies was approximately 57% at 12 months, which fell to 38.4% at three years. Studies included were heterogeneous in nature with respect to treatment setting, type of OST, risk factor assessment, ascertainment of outcome and duration of follow-up. While the presence of such methodological heterogeneity makes it difficult to synthesise results, there is limited evidence to support the influence of a number of factors on retention, including age, substance use, OST drug dose, legal issues, and attitudes to OST., Conclusions: Younger age, substance use particularly cocaine and heroin use, lower doses of methadone, criminal activity/incarceration, and negative attitudes to MMT appear to be associated with reduced retention in OST. A consensus definition of retention is required to allow for comparability across future studies., Competing Interests: The authors have declared that no competing interests exist.

In clinical trials and observational studies, the effect of an intervention or exposure can be reported as an absolute or relative comparative measure such as risk difference, odds ratio or risk ratio, or at the group level with the estimated risk of disease in each group. For meta-analysis of results with covariate adjustment, the log of the odds ratio (log odds ratio), with its standard error, is a commonly used measure of effect. However, extracting the adjusted log odds ratio from the reported estimates of disease risk in each group is not straightforward. Here, we propose a method to transform the adjusted probability of the event in each group to the log of the odds ratio and obtain the appropriate (approximate) standard error, which can then be used in a meta-analysis. We also use example data to compare our method with two other methods and show that our method is superior in calculating the standard error of the log odds ratio., Competing Interests: The authors have declared that no competing interests exist.

Evidence-based decision making is a hallmark of effective veterinary clinical practice. Scoping reviews, systematic reviews, and meta-analyses all are methods intended to provide transparent and replicable ways of summarizing a body of research to address an important clinical or public health issue. As these methods increasingly are being used by researchers and read by practitioners, it is important to understand the distinction between these techniques and to understand what research questions they can, and cannot, address. This review provides an overview of scoping reviews, systematic reviews, and meta-analysis, including a discussion of the method and uses. A sample dataset and coding to conduct a simple meta-analysis in the statistical program R also are provided. Scoping reviews are a descriptive approach, designed to chart the literature around a particular topic. The approach involves an extensive literature search, following by a structured mapping, or charting, of the literature. The results of scoping reviews can help to inform future research by identifying gaps in the existing literature and also can be used to identify areas where there may be a sufficient depth of literature to warrant a systematic review. Systematic reviews are intended to address a specific question by identifying and summarizing all of the available research that has addressed the review question. Questions types that can be addressed by a systematic review include prevalence/incidence questions, and questions related to etiology, intervention efficacy, and diagnostic test accuracy. The systematic review process follows structured steps with multiple reviewers working in parallel to reduce the potential for bias. An extensive literature search is undertaken and, for each relevant study identified by the search, a formal extraction of data, including the effect size, and assessment of the risk of bias is performed. The results from multiple studies can be combined using meta-analysis. Meta-analysis provides a summary effect size, and allows heterogeneity of effect among studies to be quantified and explored. These evidence synthesis approaches can provide scientific input to evidence-based clinical decision-making for veterinarians and regulatory bodies, and also can be useful for identifying gaps in the literature to enhance the efficiency of future research in a topic area., (Copyright © 2020 Sargeant and O'Connor.)

Although 90% of BRD relapses are reported to receive retreatment with a different class of antimicrobial, studies examining the impact of antimicrobial selection (i.e. bactericidal or bacteriostatic) on retreatment outcomes and the emergence of antimicrobial resistance (AMR) are deficient in the published literature. This survey was conducted to determine the association between antimicrobial class selection for treatment and retreatment of BRD relapses on antimicrobial susceptibility of Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni. Pathogens were isolated from samples submitted to the Iowa State University Veterinary Diagnostic Laboratory from January 2013 to December 2015. A total of 781 isolates with corresponding animal case histories, including treatment protocols, were included in the analysis. Original susceptibility testing of these isolates for ceftiofur, danofloxacin, enrofloxacin, florfenicol, oxytetracycline, spectinomycin, tilmicosin, and tulathromycin was performed using Clinical and Laboratory Standards Institute guidelines. Data were analyzed using a Bayesian approach to evaluate whether retreatment with antimicrobials of different mechanistic classes (bactericidal or bacteriostatic) increased the probability of resistant BRD pathogen isolation in calves. The posterior distribution we calculated suggests that an increased number of treatments is associated with a greater probability of isolates resistant to at least one antimicrobial. Furthermore, the frequency of resistant BRD bacterial isolates was greater with retreatment using antimicrobials of different mechanistic classes than retreatment with the same class. Specifically, treatment protocols using a bacteriostatic drug first followed by retreatment with a bactericidal drug were associated with a higher frequency of resistant BRD pathogen isolation. In particular, first treatment with tulathromycin (bacteriostatic) followed by ceftiofur (bactericidal) was associated with the highest probability of resistant M. haemolytica among all antimicrobial combinations. These observations suggest that consideration should be given to antimicrobial pharmacodynamics when selecting drugs for retreatment of BRD. However, prospective studies are needed to determine the clinical relevance to antimicrobial stewardship programs in livestock production systems., Competing Interests: JFC has been a consultant for Intervet-Schering Plough Animal Health (now Merck Animal Health), Bayer Animal Health, Boehringer-Ingelheim Vetmedica, Zoetis Animal Health, Midwest Veterinary Services, and Norbrook Laboratories Ltd. Author JFC is supported by the Agriculture and Food Research Initiative Competitive Grants no. 2017-67015-27124 and 2019-04991 from the USDA National Institute of Food and Agriculture and served as USDA NIFA Grant Panel Manager from 2017- 2018. AOC has been a consultant for Bayer Animal Health. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials. There are no patents, products in development, or marketed products to declare.

A systematic review and network meta-analysis (NMA) were conducted to address the question, 'What is the efficacy of litter management strategies to reduce morbidity, mortality, condemnation at slaughter, or total antibiotic use in broilers?' Eligible studies were clinical trials published in English evaluating the efficacy of litter management in broilers on morbidity, condemnations at slaughter, mortality, or total antibiotic use. Multiple databases and two conference proceedings were searched for relevant literature. After relevance screening and data extraction, there were 50 trials evaluating litter type, 22 trials evaluating litter additives, 10 trials comparing fresh to re-used litter, and six trials evaluating floor type. NMAs were conducted for mortality (61 trials) and for the presence or absence of footpad lesions (15 trials). There were no differences in mortality among the litter types, floor types, or additives. For footpad lesions, peat moss appeared beneficial compared to straw, based on a small number of comparisons. In a pairwise meta-analysis, there was no association between fresh versus used litter on the risk of mortality, although there was considerable heterogeneity among studies (I2 = 66%). There was poor reporting of key design features in many studies, and analyses rarely accounted for non-independence of observations within flocks.

Livestock producers are encouraged to reduce the use of antibiotics belonging to classes of medical importance to humans. We conducted a scoping review on non-antibiotic interventions in the form of products or management practices that could potentially reduce the need for antibiotics in beef and veal animals living under intensive production conditions. Our objectives were to systematically describe the research on this broad topic, identify specific topics that could feasibly support systematic reviews, and identify knowledge gaps. Multiple databases were searched. Two reviewers independently screened and charted the data. From the 13,598 articles screened, 722 relevant articles were charted. The number of relevant articles increased steadily from 1990. The Western European research was dominated by veal production studies whereas the North American research was dominated by beef production studies. The interventions and outcomes measured were diverse. The four most frequent interventions included non-antibiotic feed additives, vaccinations, breed type, and feed type. The four most frequent outcomes were indices of immunity, non-specific morbidity, respiratory disease, and mortality. There were seven topic areas evaluated in clinical trials that may share enough commonality to support systemic reviews. There was a dearth of studies in which interventions were compared to antibiotic comparison groups.

A systematic review and network meta-analysis were conducted to assess the relative efficacy of antimicrobial therapy given to dairy cows at dry-off. Eligible studies were controlled trials assessing the use of antimicrobials compared to no treatment or an alternative treatment, and assessed one or more of the following outcomes: incidence of intramammary infection (IMI) at calving, incidence of IMI during the first 30 days in milk (DIM), or incidence of clinical mastitis during the first 30 DIM. Databases and conference proceedings were searched for relevant articles. The potential for bias was assessed using the Cochrane Risk of Bias 2.0 algorithm. From 3480 initially identified records, 45 trials had data extracted for one or more outcomes. Network meta-analysis was conducted for IMI at calving. The use of cephalosporins, cloxacillin, or penicillin with aminoglycoside significantly reduced the risk of new IMI at calving compared to non-treated controls (cephalosporins, RR = 0.37, 95% CI 0.23-0.65; cloxacillin, RR = 0.55, 95% CI 0.38-0.79; penicillin with aminoglycoside, RR = 0.42, 95% CI 0.26-0.72). Synthesis revealed challenges with a comparability of outcomes, replication of interventions, definitions of outcomes, and quality of reporting. The use of reporting guidelines, replication among interventions, and standardization of outcome definitions would increase the utility of primary research in this area.