24 results on '"Camilla Birkegård"'
Search Results
2. Efficacy and Safety Analyses of Recombinant Factor VIIa in Severe Post-Partum Hemorrhage
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Camila Caram-Deelder, Hellen McKinnon Edwards, Jarmila A. Zdanowicz, Thomas van den Akker, Camilla Birkegård, Jan Blatný, Johanna G. van der Bom, Giuseppe Colucci, Derek van Duuren, Nan van Geloven, Dacia D. C. A. Henriquez, Marian Knight, Lars Korsholm, Andrea Landorph, Géraldine Lavigne Lissalde, Zoe K. McQuilten, Daniel Surbek, Cameron Wellard, Erica M. Wood, and Frederic J. Mercier
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recombinant activated factor VII ,post-partum hemorrhage ,pregnancy complications ,hematologic ,coagulants ,therapeutic use ,Medicine - Abstract
Background: Despite a range of available treatments, it is still sometimes challenging to treat patients with severe post-partum hemorrhage (sPPH). Objective: This study evaluated the efficacy and safety of recombinant activated factor VIIa (rFVIIa) in sPPH management. Methods: An open-label, multi-center, randomized controlled trial (RCT; NCT00370877) and four observational studies (OS; OS-1 (NCT04723979), OS-2, OS-3, and OS-4) were analyzed regarding efficacy (need for subsequent invasive procedures, including uterine compression sutures, uterine or iliac artery ligations, arterial embolization, or hysterectomy) and safety (incidence of thromboembolic events (TE) and maternal mortality) of rFVIIa for sPPH. The RCT, and OS-1 and OS-2, included a control group of women who did not receive rFVIIa (with propensity score-matching used in OS-1 and OS-2), whereas OS-3 and OS-4 provided descriptive data for rFVIIa-exposed women only. Results: A total of 446 women exposed to rFVIIa and 1717 non-exposed controls were included. In the RCT, fewer rFVIIa-exposed women (50% [21/42]) had an invasive procedure versus non-exposed women (91% [38/42]; odds ratio: 0.11; 95% confidence interval: 0.03–0.35). In OS-1, more rFVIIa-exposed women (58% [22/38]) had an invasive procedure versus non-exposed women (35% [13.3/38]; odds ratio: 2.46; 95% confidence interval: 1.06–5.99). In OS-2, 17% (3/18) of rFVIIa-exposed women and 32% (5.6/17.8) of non-exposed women had an invasive procedure (odds ratio: 0.33; 95% confidence interval: 0.03–1.75). Across all included women, TEs occurred in 1.5% (0.2% arterial and 1.2% venous) of rFVIIa-exposed women and 1.6% (0.2% arterial and 1.4% venous) of non-exposed women with available data. Conclusions: The positive treatment effect of rFVIIa on the RCT was not confirmed in the OS. However, the safety analysis did not show any increased incidence of TEs with rFVIIa treatment.
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- 2024
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3. Systematic Literature Review Shows Gaps in Data on Global Prevalence and Birth Prevalence of Sickle Cell Disease and Sickle Cell Trait: Call for Action to Scale Up and Harmonize Data Collection
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Raffaella Colombatti, Inga Hegemann, Morten Medici, and Camilla Birkegård
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sickle cell disease ,sickle cell trait ,sickle cell anemia ,sickle beta-thalassemia ,epidemiology ,Medicine - Abstract
Sickle cell disease (SCD) is an inherited monogenic disorder with high prevalence throughout sub-Saharan Africa, the Mediterranean basin, the Middle East, and India. Sources of SCD epidemiology remain scarce and fragmented. A systematic literature review (SLR) to identify peer-reviewed studies on SCD epidemiology was performed, with a search of bibliographic databases and key conference proceedings from 1 January 2010 to 25 March 2022 (congress abstracts after 2018). The SLR followed PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Meta-analyses, using a binomial normal random-effects model, were performed to estimate global and regional prevalence and birth prevalence. Of 1770 journal articles and 468 abstracts screened, 115 publications met the inclusion criteria. Prevalence was highest in Africa (~800/100,000), followed by the Middle East (~200/100,000) and India (~100/100,000), in contrast to ~30/100,000 in Europe. Birth prevalence was highest in Africa (~1000/100,000) and lowest in North America (~50/100,000) and Europe (~30/100,000). This SLR confirmed that sub-Saharan and North-East Africa, India, the Middle East, and the Caribbean islands are global SCD hotspots. Publications including mortality data were sparse, and no conclusions could be drawn about mortality. The identified data were limited due to gaps in the published literature for large parts of the world population; the inconsistent reporting of SCD genotypes, diagnostic criteria, and settings; and a sparsity of peer-reviewed publications from countries with assumed high prevalence. This SLR demonstrated a lack of systematic knowledge and a need to provide uniform data collection on SCD prevalence and mortality.
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- 2023
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4. Effect of tetracycline treatment regimens on antibiotic resistance gene selection over time in nursery pigs
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Kaare Græsbøll, Inge Larsen, Julie Clasen, Anna Camilla Birkegård, Jens Peter Nielsen, Lasse Engbo Christiansen, John Elmerdahl Olsen, Øystein Angen, and Anders Folkesson
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Oxytetracycline ,Resistance genes ,qPCR ,Nursery pigs ,Microbiology ,QR1-502 - Abstract
Abstract Background The majority of antimicrobials given during the production of pigs are given to nursery pigs. The influence of antimicrobial use on the levels of antimicrobial resistant (AMR) genes is important to quantify to be able to assess the impact of resistance on the food chain and risk to human and animal health. Results This study investigated the response on the levels of nine AMR genes to five different treatment strategies with oxytetracycline, and the dynamics of gene abundance over time by following 1167 pigs from five different farms in Denmark. The results showed no significant difference between treatments and an increase in abundance for the efflux pump encoding tet(A) gene and the genes encoding the ribosomal protection proteins tet(O) and tet(W) tetracycline resistant genes following treatment, while tet(M) showed no response to treatment. However, it was also observed that the levels of tet(O), tet(W), and ermB in some farms would drift more over time compared to a single treatment-course with antibiotic. Conclusion This study underlines the large variation in AMR levels under natural conditions and the need for increased investigation of the complex interactions of antimicrobial treatment and other environmental and managerial practices in swine production on AMR gene abundance.
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- 2019
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5. Send more data: a systematic review of mathematical models of antimicrobial resistance
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Anna Camilla Birkegård, Tariq Halasa, Nils Toft, Anders Folkesson, and Kaare Græsbøll
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Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background Antimicrobial resistance is a global health problem that demands all possible means to control it. Mathematical modelling is a valuable tool for understanding the mechanisms of AMR development and spread, and can help us to investigate and propose novel control strategies. However, it is of vital importance that mathematical models have a broad utility, which can be assured if good modelling practice is followed. Objective The objective of this study was to provide a comprehensive systematic review of published models of AMR development and spread. Furthermore, the study aimed to identify gaps in the knowledge required to develop useful models. Methods The review comprised a comprehensive literature search with 38 selected studies. Information was extracted from the selected papers using an adaptation of previously published frameworks, and was evaluated using the TRACE good modelling practice guidelines. Results None of the selected papers fulfilled the TRACE guidelines. We recommend that future mathematical models should: a) model the biological processes mechanistically, b) incorporate uncertainty and variability in the system using stochastic modelling, c) include a sensitivity analysis and model external and internal validation. Conclusion Many mathematical models of AMR development and spread exist. There is still a lack of knowledge about antimicrobial resistance, which restricts the development of useful mathematical models.
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- 2018
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6. Associations between Antibacterial Treatment and the Prevalence of Tail-Biting-Related Sequelae in Danish Finishers at Slaughter
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Mette Fertner, Matt Denwood, Anna Camilla Birkegård, Helle Stege, and Anette Boklund
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slaughter remarks ,pigs ,swine ,meat inspection ,hierarchical model ,antibiotic use ,Veterinary medicine ,SF600-1100 - Abstract
Secondary infections as a result of tail biting cause substantial economic losses in pig production and are a subject of concern for animal welfare. The use of first-choice antibacterial agents in the treatment of tail biting in finishing pigs is hypothesized to be negatively correlated with the development of systemic infection. This would be expected to reduce the prevalence of post-mortem pyemic sequelae (such as osteomyelitis and abscesses) in finishers with tail-bite lesions. We performed a register-based study that included three Danish databases, holding information on the purchase of antibacterials at herd level (VetStat), herd demographics (Central Husbandry Register), and relevant observations at slaughter (meat inspection data). We included all finishers from indoor production finisher herds that met the inclusion criterion of at least one slaughtered finisher with a recorded tail-bite observation during 2015 at the single largest Danish abattoir. The final dataset held 1,070 herds with one or more tail-bite observations, from which 14,411 of 2,906,626 finishers (0.50%) had an individual record of a tail bite. Within this group of finishers with tail-bite observations, the recorded tail-biting-related sequelae included osteomyelitis (8.1%), abscesses in the hindquarters (10.5%), abscesses in the forequarters (2.3%), abscesses in the mid-section of the carcass (2.9%), abscesses in the limbs (2.4%), and chronic arthritis (0.5%). Due to a high-herd prevalence (>25%), osteomyelitis and abscesses in the hindquarters were selected for further analysis. The occurrence of osteomyelitis and hindquarter abscesses in individual finishers with tail-bite observations was described using a generalized linear mixed effects model with binomial response and logit link. Herd was included as a random effect, while herd size and various antibacterial treatments were tested for inclusion in the model as fixed effects. The final models indicated a significant association between herd size and both osteomyelitis (p = 0.014) and hindquarter abscesses (p
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- 2017
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7. Evolution of TEM-type extended-spectrum β-lactamases in Escherichia coli by cephalosporins
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Anna Camilla Birkegård, Julie Clasen, Anders Folkesson, and Kaare Græsbøll
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Microbiology (medical) ,Cefotaxime ,medicine.drug_class ,Immunology ,Cephalosporin ,Ceftazidime ,Microbial Sensitivity Tests ,Biology ,Microbiology ,beta-Lactamases ,Evolution, Molecular ,Antibiotic resistance ,Drug Resistance, Multiple, Bacterial ,Escherichia coli ,polycyclic compounds ,medicine ,Humans ,Immunology and Allergy ,Ceftibuten ,Etest ,Experimental evolution ,Ceftriaxone ,Sequence Analysis, DNA ,biochemical phenomena, metabolism, and nutrition ,bacterial infections and mycoses ,Anti-Bacterial Agents ,Cephalosporins ,Mutation ,bacteria ,medicine.drug - Abstract
Objectives This study was conducted to examine the molecular mechanisms responsible for the evolution of TEM-type extended-spectrum β-lactamases (ESBLs) following selective pressure from four third-generation cephalosporins, namely ceftazidime, cefotaxime, ceftriaxone and ceftibuten. In addition, selective enrichment for ESBL detection in environmental samples was investigated. Methods Using experimental evolution, resistant variants were isolated and mutations in TEM-1 were examined by DNA sequencing. Resistance levels and the development of cross-resistance were determined for ESBL-producing isolates by Etest and disk diffusion assay. Selective plating with or without prior growth in selective broth was used to examine the approach of selective enrichment for ESBL detection. Results The third-generation cephalosporins ceftazidime, cefotaxime and ceftriaxone selected for ESBLs, whereas ceftibuten did not. All ESBL variants additionally remained susceptible to ceftibuten. DNA sequencing of the TEM-1 coding sequence of mutants revealed mutations not previously isolated through selection. This indicates that the potential for ESBL evolution is much broader than can be inferred from sequence analysis of clinical samples alone. The results also indicate that selective enrichment for enhanced detection of ESBL-producers may give unreliable results owing to the selection of spontaneous mutations in narrow-spectrum β-lactamases resulting in TEM-type ESBL-producers. Conclusion These results help explain the molecular changes responsible for evolution of TEM-type ESBLs and meanwhile question the appropriate use of selective enrichment for detection of ESBLs in environmental samples.
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- 2019
8. Long-Term Effectiveness and Safety of Childhood Growth Hormone Treatment in Noonan Syndrome
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Petur Benedikt Juliusson, Alicia A Romano, Judith L. Ross, Tilman R Rohrer, Bradley S. Miller, Michel Polak, Jennifer Abuzzahab, Lars Sävendahl, Vlady Ostrow, Alberto Pietropoli, Joanne C. Blair, Anna Camilla Birkegård, Philippe Backeljauw, and Jovanna Dahlgren
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Male ,Aging ,medicine.medical_specialty ,Adolescent ,Childhood growth ,Endocrinology, Diabetes and Metabolism ,Scoliosis ,Growth hormone ,Gastroenterology ,Cohort Studies ,Child Development ,Endocrinology ,Internal medicine ,medicine ,Humans ,Longitudinal Studies ,Drug reaction ,Child ,Adverse effect ,Human Growth Hormone ,business.industry ,Noonan Syndrome ,Age Factors ,medicine.disease ,Body Height ,Treatment Outcome ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Gh treatment ,Noonan syndrome ,Female ,business ,Hormone - Abstract
Introduction: Few data exist on long-term growth hormone (GH) treatment in patients with Noonan syndrome (NS). Objective: To evaluate the effectiveness and safety of GH treatment in NS in clinical practice. Methods: Height gain, near-adult height (NAH), and safety were assessed in 2 complementary non-interventional studies: NordiNet® IOS and ANSWER. The safety analysis included 412 patients, and the effectiveness analysis included 84 GH-treated patients (male, n = 67) with ≥4 years’ height standard deviation score (HSDS) data. HSDS was determined using national reference (NR) and NS-specific (NSS) data. Results: The mean (SD) baseline age was 8.38 (3.57) years; HSDS, −2.76 (1.03); GH dose, 41.6 (11.1) µg/kg/day. The mean (SD) HSDS increase from baseline (ΔHSDS) was 0.49 (0.37) (first year), 0.79 (0.58) (second year), and 1.01 (0.60) (third year) (NR). The mean (SD) HSDS at year 3 was −1.66 (1.00) (NR; 1.06 [1.12] [NSS]). Twenty-four patients achieved NAH. The mean (SD) NAH SDS (NR) was −1.51 (0.60) (154.90 [3.21] cm) in females and −1.79 (1.09) (165.61 [7.19] cm) in males; 70.8% (17/24) had NAH SDS ≥ −2. Adverse drug reactions and GH-unrelated serious adverse events (n = 34) were reported in 22/412 (5.3%) patients. Four neoplasms and 3 cases of scoliosis were reported; no cardiovascular adverse events occurred. Conclusions: GH-treated children with NS achieved substantial height gain during the first 3 years of follow-up. Overall, 24 patients achieved NAH, with 70.8% having NAH SDS ≥ –2. There was no evidence to support a higher prevalence of neoplasm, or cardiac or other comorbidities.
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- 2021
9. Predicting effects of changed antimicrobial usage on the abundance of antimicrobial resistance genes in finisher’ gut microbiomes
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Frank Møller Aarestrup, Berith Elkær Knudsen, Patrick Munk, Valeria Bortolaia, M. S. Jensen, L. V. De Knegt, Anna Camilla Birkegård, Oksana Lukjancenko, Håkan Vigre, and Vibe Dalhoff Andersen
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Farms ,040301 veterinary sciences ,Denmark ,Sus scrofa ,030231 tropical medicine ,Resistance ,Drug resistance ,Biology ,Predictive ,Modelling ,0403 veterinary science ,Toxicology ,03 medical and health sciences ,0302 clinical medicine ,Antibiotic resistance ,Food Animals ,Abundance (ecology) ,Drug Resistance, Bacterial ,Animals ,Sequencing ,Microbiome ,Animal Husbandry ,Antiinfective agent ,04 agricultural and veterinary sciences ,Antimicrobial ,Anti-Bacterial Agents ,Gastrointestinal Microbiome ,Animal Science and Zoology ,Observational study ,Pigs ,Predictive modelling - Abstract
It is accepted that usage of antimicrobials (AMs) in food animals causes the emergence and spread of antimicrobial resistance (AMR) in this sector, while also contributing to the burden of AMR in humans. Curbing the increasing occurrence of AMR in food animals requires in-depth knowledge of the quantitative relationship between antimicrobial usage (AMU) and AMR to achieve desired resistance reductions from interventions targeting AMU. In the observational study, the relationships between lifetime AMU in 83 finisher batches from Danish farms and the AMR gene abundances of seven antimicrobial classes in their gut microbiomes were quantified using multi-variable linear regression models. These relationships and the national lifetime AMU in pigs were included in the predictive modelling that allowed for testing of scenarios with changed lifetime AMU for finishers produced in Denmark in 2014. A total of 50 farms from the observational study were included in validating the observational study and the predictive modelling. The results from the observational study showed that the relationship was linear, and that the parenteral usage of AMs had a high effect on specific AM-classes of resistance, whereas the peroral usage had a lower but broader effect on several classes. Three different scenarios of changed lifetime AMU were simulated in the predictive modelling. When all tetracycline usage ceased, the predicted interval reductions of aminoglycoside, lincosamide and tetracycline resistance were 4–42 %, 0–8 % and 9–18 %, respectively. When the peroral tetracycline usage of the 10 % highest users was replaced with peroral macrolide usage, the tetracycline resistance fell by 1–2 % and the macrolide and MLSb resistance increased by 5–8 %. When all extended-spectrum penicillin usage was replaced with parenteral lincosamide usage, the beta-lactam resistance fell by 2–7 %, but the lincosamide usage and resistance increased by 194 % and 10–45 %, respectively. The external validation provided results within the 95 % CI of the predictive modelling outcome at national level, while the external validation at farm level was less accurate. In conclusion, interventions targeting AMU will reduce AMR abundance, though differently depending on the targeted AM-class and provided the reduction of one AM-class usage is not replaced with usage of another AM-class. Predicting several classes of AMR gene abundance simultaneously will support stakeholders when deciding on interventions targeting AMU in the finisher production to avoid adverse and unforeseen effects on the AMR abundance. This study provides a sound predictive modelling framework for further development, including the dynamics of AMU on AMR in finishers at national level.
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- 2020
10. Pregnancy outcomes in women receiving growth hormone therapy enrolled in NordiNet international outcome study (IOS) and American Norditropin Studies: Web Enabled Research (ANSWER Program)
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Biller, Beverly, primary, Höybye, Charlotte, additional, Camilla, Birkegård Anna, additional, Pietropoli, Alberto, additional, and Weber, Matthias, additional
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- 2020
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11. Association between selected antimicrobial resistance genes and antimicrobial exposure in Danish pig farms
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Anders Folkesson, Kaare Græsbøll, Anna Camilla Birkegård, Tariq Hisham Beshara Halasa, Julie Clasen, and Nils Toft
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0301 basic medicine ,Veterinary medicine ,Farms ,Individual gene ,Swine ,Denmark ,030106 microbiology ,lcsh:Medicine ,Biology ,Antimicrobial resistance ,Article ,03 medical and health sciences ,Feces ,Antibiotic resistance ,Anti-Infective Agents ,SDG 3 - Good Health and Well-being ,Animals ,Selection, Genetic ,Pig farms ,lcsh:Science ,Gene ,Lifetime exposure ,Swine Diseases ,Multidisciplinary ,lcsh:R ,Drug Resistance, Microbial ,Environmental Exposure ,Antimicrobial ,030104 developmental biology ,Risk factors ,Genes, Bacterial ,Antimicrobial resistance genes ,lcsh:Q - Abstract
Bacterial antimicrobial resistance (AMR) in pigs is an important public health concern due to its possible transfer to humans. We aimed at quantifying the relationship between the lifetime exposure of antimicrobials and seven antimicrobial resistance genes in Danish slaughter pig farms. AMR gene levels were quantified by qPCR of total-community DNA in faecal samples obtained from 681 batches of slaughter pigs. The lifetime exposure to antimicrobials was estimated at batch level for the piglet, weaner, and finisher periods individually for the sampled batches. We showed that the effect of antimicrobial exposure on the levels of AMR genes was complex and unique for each individual gene. Several antimicrobial classes had both negative and positive correlations with the AMR genes. From 10–42% of the variation in AMR gene levels could be explained in the final regression models, indicating that antimicrobial exposure is not the only important determinant of the AMR gene levels.
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- 2017
12. Continuing occurrence of vancomycin resistance determinants in Danish pig farms 20 years after removing exposure to avoparcin
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Anders Folkesson, Tariq Hisham Beshara Halasa, Nils Toft, Anna Camilla Birkegård, Kaare Græsbøll, and Julie Clasen
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Veterinary medicine ,Farms ,Livestock ,Swine ,Denmark ,animal diseases ,Avoparcin ,Microbial Sensitivity Tests ,Biology ,Antimicrobial resistance ,Microbiology ,Danish ,03 medical and health sciences ,chemistry.chemical_compound ,Feces ,Antibiotic resistance ,Bacterial Proteins ,medicine ,Enterococcus spp ,Animals ,Pig farms ,Carbon-Oxygen Ligases ,030304 developmental biology ,Vancomycin resistance ,0303 health sciences ,General Veterinary ,030306 microbiology ,business.industry ,Glycopeptides ,Drug Resistance, Microbial ,Vancomycin Resistance ,General Medicine ,biochemical phenomena, metabolism, and nutrition ,language.human_language ,Anti-Bacterial Agents ,chemistry ,language ,Vancomycin ,Female ,business ,Enterococcus ,medicine.drug - Abstract
Vancomycin-resistant Enterococcus spp. is a major health problem worldwide and livestock have been implicated in constituting a reservoir for the transmission of vancomycin resistance to zoonotic pathogens. Vancomycin resistance determinants can be situated on mobile genetic elements and transferred between bacterial species The livestock reservoir must therefore be included in a risk assessment of the vancomycin resistance burden. Avoparcin, a vancomycin analogue, has not been used in Danish pig production for over 20 years and vancomycin has never been used. The objective of this study was to screen faecal samples from Danish pig farms for nine selected vancomycin resistance determinants. We found at least four different vancomycin resistance determinants in all screened Danish pig farms (665 finisher farms and 78 sow farms). The vancomycin resistance determinants present in vanB or vanG clusters were found at significantly different levels in sow and finisher farms. However, vanA was not detected in any of the farms. In conclusion, vancomycin resistance determinants are still present in Danish pig production 25 years after the ban on avoparcin use.
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- 2019
13. Effect of tetracycline treatment regimens on antibiotic resistance gene selection over time in nursery pigs
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Anders Folkesson, Lasse Engbo Christiansen, Inge Larsen, Anna Camilla Birkegård, Kaare Græsbøll, Øystein Angen, John Elmerdahl Olsen, Jens Nielsen, and Julie Clasen
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Diarrhea ,Microbiology (medical) ,Farms ,Swine ,medicine.drug_class ,Tetracycline ,Denmark ,Lawsonia Bacteria ,Antibiotics ,lcsh:QR1-502 ,Oxytetracycline ,Resistance genes ,Biology ,Microbiology ,lcsh:Microbiology ,Feces ,03 medical and health sciences ,SDG 3 - Good Health and Well-being ,medicine ,Animals ,Animal Husbandry ,Gene ,030304 developmental biology ,Swine Diseases ,0303 health sciences ,Bacteria ,030306 microbiology ,Tetracycline Resistance ,Ribosomal RNA ,Antimicrobial ,Anti-Bacterial Agents ,Desulfovibrionaceae Infections ,qPCR ,Parasitology ,Nursery pigs ,Efflux ,Genes, MDR ,Research Article ,medicine.drug - Abstract
Background The majority of antimicrobials given during the production of pigs are given to nursery pigs. The influence of antimicrobial use on the levels of antimicrobial resistant (AMR) genes is important to quantify to be able to assess the impact of resistance on the food chain and risk to human and animal health. Results This study investigated the response on the levels of nine AMR genes to five different treatment strategies with oxytetracycline, and the dynamics of gene abundance over time by following 1167 pigs from five different farms in Denmark. The results showed no significant difference between treatments and an increase in abundance for the efflux pump encoding tet(A) gene and the genes encoding the ribosomal protection proteins tet(O) and tet(W) tetracycline resistant genes following treatment, while tet(M) showed no response to treatment. However, it was also observed that the levels of tet(O), tet(W), and ermB in some farms would drift more over time compared to a single treatment-course with antibiotic. Conclusion This study underlines the large variation in AMR levels under natural conditions and the need for increased investigation of the complex interactions of antimicrobial treatment and other environmental and managerial practices in swine production on AMR gene abundance.
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- 2019
14. Determining the optimal number of individual samples to pool for quantification of average herd levels of antimicrobial resistance genes in Danish pig herds using high-throughput qPCR
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Anders Folkesson, Tariq Hisham Beshara Halasa, Anna Camilla Birkegård, John Elmerdahl Olsen, Julie Clasen, Nils Toft, Anders Mellerup, and Øystein Angen
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0301 basic medicine ,Veterinary medicine ,Future studies ,040301 veterinary sciences ,Denmark ,Sus scrofa ,030106 microbiology ,Pooling ,Sample (statistics) ,Biology ,Real-Time Polymerase Chain Reaction ,Microbiology ,0403 veterinary science ,Feces ,03 medical and health sciences ,Anti-Infective Agents ,Drug Resistance, Bacterial ,Animals ,Animal Husbandry ,Genetics ,General Veterinary ,Reproducibility of Results ,04 agricultural and veterinary sciences ,General Medicine ,Genes, Bacterial ,Sample size determination ,Herd ,Antimicrobial resistance genes - Abstract
The primary objective of this study was to determine the minimum number of individual fecal samples to pool together in order to obtain a representative sample for herd level quantification of antimicrobial resistance (AMR) genes in a Danish pig herd, using a novel high-throughput qPCR assay. The secondary objective was to assess the agreement between different methods of sample pooling. Quantification of AMR was achieved using a high-throughput qPCR method to quantify the levels of seven AMR genes (ermB, ermF, sulI, sulII, tet(M), tet(O) and tet(W)). A large variation in the levels of AMR genes was found between individual samples. As the number of samples in a pool increased, a decrease in sample variation was observed. It was concluded that the optimal pooling size is five samples, as an almost steady state in the variation was observed when pooling this number of samples. Good agreement between different pooling methods was found and the least time-consuming method of pooling, by transferring feces from each individual sample to a tube using a 10μl inoculation loop and adding 3.5ml of PBS, approximating a 10% solution, can therefore be used in future studies.
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- 2016
15. Send more data: a systematic review of mathematical models of antimicrobial resistance
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Kaare Græsbøll, Anna Camilla Birkegård, Anders Folkesson, Nils Toft, and Tariq Hisham Beshara Halasa
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0301 basic medicine ,Microbiology (medical) ,Stochastic modelling ,030106 microbiology ,Review ,lcsh:Infectious and parasitic diseases ,03 medical and health sciences ,Anti-Infective Agents ,Medicine ,Animals ,Humans ,Pharmacology (medical) ,Lack of knowledge ,lcsh:RC109-216 ,Public Health Surveillance ,Internal validation ,Adaptation (computer science) ,TRACE (psycholinguistics) ,Mathematical model ,business.industry ,Public Health, Environmental and Occupational Health ,Reproducibility of Results ,Drug Resistance, Microbial ,Models, Theoretical ,030104 developmental biology ,Infectious Diseases ,Risk analysis (engineering) ,Meta-analysis ,business - Abstract
Background Antimicrobial resistance is a global health problem that demands all possible means to control it. Mathematical modelling is a valuable tool for understanding the mechanisms of AMR development and spread, and can help us to investigate and propose novel control strategies. However, it is of vital importance that mathematical models have a broad utility, which can be assured if good modelling practice is followed. Objective The objective of this study was to provide a comprehensive systematic review of published models of AMR development and spread. Furthermore, the study aimed to identify gaps in the knowledge required to develop useful models. Methods The review comprised a comprehensive literature search with 38 selected studies. Information was extracted from the selected papers using an adaptation of previously published frameworks, and was evaluated using the TRACE good modelling practice guidelines. Results None of the selected papers fulfilled the TRACE guidelines. We recommend that future mathematical models should: a) model the biological processes mechanistically, b) incorporate uncertainty and variability in the system using stochastic modelling, c) include a sensitivity analysis and model external and internal validation. Conclusion Many mathematical models of AMR development and spread exist. There is still a lack of knowledge about antimicrobial resistance, which restricts the development of useful mathematical models.
- Published
- 2018
16. Building the foundation for veterinary register-based epidemiology: A systematic approach to data quality assessment and validation
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Anna Camilla Birkegård, Nils Toft, Tariq Hisham Beshara Halasa, Anette Boklund, Vibeke Frøkjær Jensen, Ana Carolina Lopes Antunes, and Mette Ely Fertner
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0301 basic medicine ,Veterinary Medicine ,Veterinary medicine ,medicine.medical_specialty ,Farms ,Databases, Factual ,040301 veterinary sciences ,Epidemiology ,Computer science ,Swine ,media_common.quotation_subject ,Denmark ,030106 microbiology ,0403 veterinary science ,Danish ,03 medical and health sciences ,medicine ,Animals ,Humans ,Quality (business) ,Registries ,media_common ,Measure (data warehouse) ,General Veterinary ,General Immunology and Microbiology ,Public Health, Environmental and Occupational Health ,Foundation (evidence) ,04 agricultural and veterinary sciences ,language.human_language ,Data Accuracy ,Infectious Diseases ,Workflow ,Register (music) ,Research Design ,Data quality ,language ,Epidemiologic Methods - Abstract
Epidemiological studies often use data from registers. Data quality is of vital importance for the quality of the research. The aim of this study was to suggest a structured workflow to assess the quality of veterinary national registers. As an example of how to use the workflow, the quality of the following three registers was assessed: the Central Husbandry Register (CHR), the database for movement of pigs (DMP) and the national Danish register of drugs for veterinary use (VetStat). A systematic quantitative assessment was performed, with calculation the proportion of farms and observations with "poor quality" of data. "Poor" quality was defined for each measure (variable) either as a mismatch between and/or within registers, registrations of numbers outside the expected range, or unbalanced in- and outgoing movements. Interviews were conducted to make a complementary qualitative assessment. The proportion of farms and observations within each quality measure varied. This study highlights the importance of systematic quality assessment of register data and suggests a systematic approach for such assessments and validations without the use of primary data.
- Published
- 2018
17. Persistence of antimicrobial resistance genes from sows to finisher pigs
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Anna Camilla Birkegård, Tariq Hisham Beshara Halasa, Nils Toft, Julie Clasen, Anders Folkesson, and Kaare Græsbøll
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0301 basic medicine ,Veterinary medicine ,040301 veterinary sciences ,Offspring ,Swine ,animal diseases ,030106 microbiology ,Finisher pig ,Biology ,Polymerase Chain Reaction ,Persistence (computer science) ,0403 veterinary science ,03 medical and health sciences ,Antibiotic resistance ,Food Animals ,Drug Resistance, Bacterial ,Animals ,Animal Husbandry ,Gene ,04 agricultural and veterinary sciences ,Anti-Bacterial Agents ,Significant positive correlation ,Antimicrobial resistance genes ,Animal Science and Zoology ,Female ,Abattoirs - Abstract
Antimicrobial resistance in pigs has been under scrutiny for many years. However, many questions remain unanswered, including whether the initial antimicrobial resistance level of a pig will influence the antimicrobial resistance found at slaughter. Faecal samples from finishers pigs from 681 farms and from sows from 82 farms were collected, and levels of seven antimicrobial resistance genes, ermB, ermF, sulI, sulII, tet(M), tet(O), and tet(W), were quantified by high-capacity qPCR. There were 40 pairs of observations where the finishers were born in the farms of the sows. The objective of this study was to evaluate whether the levels of AMR genes found in finisher pigs at slaughter were associated with the levels in the farm where the finishers were born, and whether the levels of the AMR genes were equal in the sow and finisher pig populations. We found a significant positive correlation between the levels of AMR genes in finishers and the sows in the farms where the pigs were born for some of the genes (ermB (ρ=0.47, p-value=0.002), ermF (ρ=0.41, p-value=0.03), and tet(O) (ρ=0.33, p-value=0.04)). Furthermore, there were significant differences between AMR gene levels for the sow and finisher populations for ermB, ermF, sulI, sulII, tet(O), and tet(W), though not for tet(M).
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- 2017
18. Spatial patterns of antimicrobial resistance genes in a cross-sectional sample of pig farms with indoor non-organic production of finishers
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Tariq Hisham Beshara Halasa, Anna Camilla Birkegård, Håkan Vigre, Nils Toft, Julie Clasen, Anders Folkesson, and Annette Kjær Ersbøll
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0301 basic medicine ,Veterinary medicine ,040301 veterinary sciences ,Epidemiology ,Swine ,pig farms ,Denmark ,030106 microbiology ,Population ,Organic production ,Microbial Sensitivity Tests ,Biology ,Disease cluster ,Polymerase Chain Reaction ,0403 veterinary science ,03 medical and health sciences ,Feces ,Bacterial Proteins ,Drug Resistance, Bacterial ,Animals ,Animal Husbandry ,education ,Pig farms ,spatial patterns ,Swine Diseases ,education.field_of_study ,Bacteria ,business.industry ,High-Throughput Nucleotide Sequencing ,04 agricultural and veterinary sciences ,Bacterial Infections ,Original Papers ,Biotechnology ,Anti-Bacterial Agents ,Geographic distribution ,Antimicrobial resistance genes ,Infectious Diseases ,Cross-Sectional Studies ,Spatial ecology ,Common spatial pattern ,business - Abstract
SUMMARYAntimicrobial resistance (AMR) in pig populations is a public health concern. There is a lack of information of spatial distributions of AMR genes in pig populations at large scales. The objective of the study was to describe the spatial pattern of AMR genes in faecal samples from pig farms and to test if the AMR genes were spatially randomly distributed with respect to the geographic distribution of the pig farm population at risk. Faecal samples from 687 Danish pig farms were collected in February and March 2015. DNA was extracted and the levels of seven AMR genes (ermB, ermF, sulI, sulII, tet(M), tet(O) and tet(W)) were quantified on a high-throughput real-time PCR array. Spatial differences for the levels of the AMR genes measured as relative quantities were evaluated by spatial cluster analysis and creating of risk maps using kriging analysis and kernel density estimation. Significant spatial clusters were identified for ermB, ermF, sulII and tet(W). The broad spatial trends in AMR resistance evident in the risk maps were in agreement with the results of the cluster analysis. However, they also showed that there were only small scale spatial differences in the gene levels. We conclude that the geographical location of a pig farm is not a major determinant of the presence or high levels of AMR genes assessed in this study.
- Published
- 2017
19. Improving institutional memory on challenges and methods for estimation of pig herd antimicrobial exposure based on data from the Danish Veterinary Medicines Statistics Program (VetStat)
- Author
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Nana Hee Dupont, Mette Ely Fertner, Anna Camilla Birkegård, Vibe Dalhoff Andersen, Gitte Blach Nielsen, Amanda Brinch Kruse, and Leonardo Victor de Knegt
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FOS: Biological sciences ,Other Quantitative Biology (q-bio.OT) ,Quantitative Biology - Other Quantitative Biology - Abstract
With the increasing occurrence of antimicrobial resistance, more attention has been directed towards surveillance of both human and veterinary antimicrobial use. Since the early 2000s, several research papers on Danish pig antimicrobial usage have been published, based on data from the Danish Veterinary Medicines Statistics Program (VetStat). VetStat was established in 2000, as a national database containing detailed information on purchases of veterinary medicine. This paper presents a critical set of challenges originating from static system features, which researchers must address when estimating antimicrobial exposure in Danish pig herds. Most challenges presented are followed by at least one robust solution. A set of challenges requiring awareness from the researcher, but for which no immediate solution was available, were also presented. The selection of challenges and solutions was based on a consensus by a cross-institutional group of researchers working in projects using VetStat data. No quantitative data quality evaluations were performed, as the frequency of errors and inconsistencies in a dataset will vary, depending on the period covered in the data. Instead, this paper focuses on clarifying how VetStat data may be translated to an estimation of the antimicrobial exposure at herd level, by suggesting uniform methods of extracting and editing data, in order to obtain reliable and comparable estimates on pig antimicrobial consumption for research purposes., Comment: 25 pages, including two Appendices (pages not numbered). Title page, including abstract, is on page 1. Body of text, including references, abbreviation list and disclaimers for conflict of interest and funding, are on pages 2-18. Two figures embedded in the text on pages 3 and 5. Appendix 1 starts on page 19, and Appendix 2 on page 25
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- 2017
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20. Sampling pig farms at the abattoir in a cross-sectional study − Evaluation of a sampling method
- Author
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Nils Toft, Tariq Hisham Beshara Halasa, and Anna Camilla Birkegård
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0301 basic medicine ,Veterinary medicine ,Farms ,Pig farm ,040301 veterinary sciences ,Computer science ,Swine ,media_common.quotation_subject ,030106 microbiology ,Population ,Sample (statistics) ,Cross-Sectional study ,Sampling procedure ,0403 veterinary science ,03 medical and health sciences ,Food Animals ,Statistics ,Animals ,education ,media_common ,Selection bias ,Swine Diseases ,education.field_of_study ,Data collection ,Sampling (statistics) ,Reproducibility of Results ,Systematic sampling ,04 agricultural and veterinary sciences ,Simple random sample ,Bacterial Typing Techniques ,Cross-Sectional Studies ,Slaughterhouse ,Animal Science and Zoology ,Lot quality assurance sampling ,Abattoirs ,Abattoir - Abstract
A cross-sectional study design is relatively inexpensive, fast and easy to conduct when compared to other study designs. Careful planning is essential to obtaining a representative sample of the population, and the recommended approach is to use simple random sampling from an exhaustive list of units in the target population. This approach is rarely feasible in practice, and other sampling procedures must often be adopted. For example, when slaughter pigs are the target population, sampling the pigs on the slaughter line may be an alternative to on-site sampling at a list of farms. However, it is difficult to sample a large number of farms from an exact predefined list, due to the logistics and workflow of an abattoir. Therefore, it is necessary to have a systematic sampling procedure and to evaluate the obtained sample with respect to the study objective. We propose a method for 1) planning, 2) conducting, and 3) evaluating the representativeness and reproducibility of a cross-sectional study when simple random sampling is not possible. We used an example of a cross-sectional study with the aim of quantifying the association of antimicrobial resistance and antimicrobial consumption in Danish slaughter pigs. It was not possible to visit farms within the designated timeframe. Therefore, it was decided to use convenience sampling at the abattoir. Our approach was carried out in three steps: 1) planning: using data from meat inspection to plan at which abattoirs and how many farms to sample; 2) conducting: sampling was carried out at five abattoirs; 3) evaluation: representativeness was evaluated by comparing sampled and non-sampled farms, and the reproducibility of the study was assessed through simulated sampling based on meat inspection data from the period where the actual data collection was carried out. In the cross-sectional study samples were taken from 681 Danish pig farms, during five weeks from February to March 2015. The evaluation showed that the sampling procedure was reproducible with results comparable to the collected sample. However, the sampling procedure favoured sampling of large farms. Furthermore, both under-sampled and over-sampled areas were found using scan statistics. In conclusion, sampling conducted at abattoirs can provide a spatially representative sample. Hence it is a possible cost-effective alternative to simple random sampling. However, it is important to assess the properties of the resulting sample so that any potential selection bias can be addressed when reporting the findings.
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- 2017
21. Breeding Restrictions Decrease the Prevalence of Myxomatous Mitral Valve Disease in Cavalier King Charles Spaniels over an 8-to 10-Year Period
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Lisbeth H. Olsen, M.J. Reimann, Anna Camilla Birkegård, Jens Häggström, H. D. Pedersen, and Torben Martinussen
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0301 basic medicine ,medicine.medical_specialty ,040301 veterinary sciences ,Cardiology ,Disease ,Standard Article ,Breeding ,Logistic regression ,Odds ,0403 veterinary science ,03 medical and health sciences ,Dogs ,Internal medicine ,Dog ,Genetics ,Medicine ,Mitral valve prolapse ,Animals ,Genetic Predisposition to Disease ,Dog Diseases ,Myxomatous mitral valve ,Retrospective Studies ,Mitral Valve Prolapse ,Inheritance ,General Veterinary ,medicine.diagnostic_test ,business.industry ,Mitral regurgitation murmur ,04 agricultural and veterinary sciences ,Auscultation ,medicine.disease ,Standard Articles ,Surgery ,030104 developmental biology ,SMALL ANIMAL ,business ,Purebred - Abstract
Background: Cavalier King Charles Spaniels (CKCS) are predisposed to myxomatous mitral valve disease (MMVD). Studies have indicated a strong genetic background. Objective: The aim of this study was to evaluate the effect of a breeding scheme involving auscultation and echocardiography. Animals: In the Danish Kennel Club mandatory breeding scheme, 997 purebred CKCS were examined during the period 2002-2011. Each dog was evaluated 1-4 times with a total of 1,380 examinations. Methods: Auscultation and echocardiography were performed to evaluate mitral regurgitation murmur severity and degree of mitral valve prolapse (MVP). The odds of having mitral regurgitation murmur or MVP > grade 1 in 2010-2011 compared to 2002-2003 were estimated using logistic regression analysis including age and sex as covariates. Odds were estimated for dogs that were products of the breeding scheme (defined as dogs with both parents approved by the breeding scheme before breeding) and non-products of the breeding scheme (defined as dogs with at least 1 parent with unknown cardiac status). Results: In 2010-2011, the odds of having mitral regurgitation murmur were 0.27 if dogs were a product of the breeding scheme compared with dogs in 2002-2003, reflecting a 73% decreased risk (P < .0001). If non-products of the breeding scheme examined in 2010-2011 were compared with dogs in 2002-2003, no difference in odds was found (P = .49). Conclusion and Clinical Importance: A mandatory breeding scheme based on auscultation and echocardiography findings significantly decreased the prevalence of MMVD over the 8- to 10-year period. Such a breeding scheme therefore is recommended for CKCS.Background: Cavalier King Charles Spaniels (CKCS) are predisposed to myxomatous mitral valve disease (MMVD). Studies have indicated a strong genetic background. Objective: The aim of this study was to evaluate the effect of a breeding scheme involving auscultation and echocardiography. Animals: In the Danish Kennel Club mandatory breeding scheme, 997 purebred CKCS were examined during the period 2002-2011. Each dog was evaluated 1-4 times with a total of 1,380 examinations. Methods: Auscultation and echocardiography were performed to evaluate mitral regurgitation murmur severity and degree of mitral valve prolapse (MVP). The odds of having mitral regurgitation murmur or MVP > grade 1 in 2010-2011 compared to 2002-2003 were estimated using logistic regression analysis including age and sex as covariates. Odds were estimated for dogs that were products of the breeding scheme (defined as dogs with both parents approved by the breeding scheme before breeding) and non-products of the breeding scheme (defined as dogs with at least 1 parent with unknown cardiac status). Results: In 2010-2011, the odds of having mitral regurgitation murmur were 0.27 if dogs were a product of the breeding scheme compared with dogs in 2002-2003, reflecting a 73% decreased risk (P < .0001). If non-products of the breeding scheme examined in 2010-2011 were compared with dogs in 2002-2003, no difference in odds was found (P = .49). Conclusion and Clinical Importance: A mandatory breeding scheme based on auscultation and echocardiography findings significantly decreased the prevalence of MMVD over the 8- to 10-year period. Such a breeding scheme therefore is recommended for CKCS. Background: Cavalier King Charles Spaniels (CKCS) are predisposed to myxomatous mitral valve disease (MMVD). Studies have indicated a strong genetic background. Objective: The aim of this study was to evaluate the effect of a breeding scheme involving auscultation and echocardiography. Animals: In the Danish Kennel Club mandatory breeding scheme, 997 purebred CKCS were examined during the period 2002-2011. Each dog was evaluated 1-4 times with a total of 1,380 examinations. Methods: Auscultation and echocardiography were performed to evaluate mitral regurgitation murmur severity and degree of mitral valve prolapse (MVP). The odds of having mitral regurgitation murmur or MVP > grade 1 in 2010-2011 compared to 2002-2003 were estimated using logistic regression analysis including age and sex as covariates. Odds were estimated for dogs that were products of the breeding scheme (defined as dogs with both parents approved by the breeding scheme before breeding) and non-products of the breeding scheme (defined as dogs with at least 1 parent with unknown cardiac status). Results: In 2010-2011, the odds of having mitral regurgitation murmur were 0.27 if dogs were a product of the breeding scheme compared with dogs in 2002-2003, reflecting a 73% decreased risk (P < .0001). If non-products of the breeding scheme examined in 2010-2011 were compared with dogs in 2002-2003, no difference in odds was found (P = .49). Conclusion and Clinical Importance: A mandatory breeding scheme based on auscultation and echocardiography findings significantly decreased the prevalence of MMVD over the 8- to 10-year period. Such a breeding scheme therefore is recommended for CKCS.
- Published
- 2016
22. Planning a cross-sectional study of antimicrobial resistance genes in Danish pig farms
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Anna Camilla Birkegård, Tariq Halasa, and Nils Toft
- Published
- 2015
23. Comparison of individual and pooled samples for quantification of antimicrobial resistance genes in swine feces by high-throughput qPCR
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Julie Clasen, Anders Mellerup, Olsen, J. E., Øystein Angen, Sven Anders Folkesson, Tariq Halasa, Nils Toft, and Anna Camilla Birkegård
- Published
- 2015
24. Spatial patterns of Antimicrobial Resistance Genes in Danish Pig Farms
- Author
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Anna Camilla Birkegård, Ersbøll, A. K., Tariq Hisham Beshara Halasa, Julie Clasen, Anders Folkesson, Håkan Vigre, and Nils Toft
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