The effectiveness of a multifaceted, group-facilitated audit and feedback intervention to increase tranexamic acid use during total joint arthroplasty.

PURPOSE: Intraoperative tranexamic acid (TXA) is used to reduce blood loss and the need for transfusions following total hip arthroplasty (THA) and total knee arthroplasty (TKA). Despite evidence in literature and local practice protocols supporting TXA as a part of standard of care for joint arthroplasty, TXA administration is underutilized. We aimed to use group-facilitated audit and feedback as the foundation of a knowledge translation strategy to increase TXA use for THA and TKA procedures. METHODS: Anesthesiologists consented to receive two data reports summarizing their individual rates of TXA use and postoperative blood transfusions compared with site peers. Variables collected included patient demographics, TXA usage, and the frequency and volume of red blood cell transfusions administered in the 72-hr postoperative period. The facilitated feedback session discussed report findings and focused on factors contributing to local practice patterns and opportunities for change. RESULTS: Tranexamic acid use increased for THA procedures at the intervention site from 66.6 to 74.4% (absolute change, 7.9%; 95% confidence interval [CI], 2.4 to 13.3). Likewise, TXA use for TKA procedures increased from 62.4 to 82.3% (absolute change, 19.9%; 95% CI 15.0 to 25.0). CONCLUSIONS: Physicians and their teams were able to review their practice data on TXA utilization, reflect on differences compared with evidence-based guidelines, discuss findings with peers, and identify opportunities for improvement. The intervention increased the use of TXA for both TKA and THA and shifted the dosage to better align with evidence-based practice guidelines.

RéSUMé: OBJECTIF : L'acide tranexamique (ATX) peropératoire est utilisé pour réduire les pertes sanguines et les besoins transfusionnels après les arthroplasties totales de la hanche (ATH) et du genou (ATG). Malgré les données probantes et les protocoles de pratique locaux appuyant l'utilisation d'ATX dans le cadre de la norme de soins en cas d'arthroplastie, l'administration de cet agent est sous-utilisée. Notre objectif était d'utiliser l'audit et la rétroaction facilités par le groupe comme base d'une stratégie d'application des connaissances afin d'accroître l'utilisation de l'ATX lors des ATH et ATG. MéTHODE: Les anesthésiologistes ont consenti à recevoir deux rapports de données résumant leurs taux individuels d'utilisation d'ATX et de transfusions sanguines postopératoires par rapport à leurs pairs au sein du même établissement. Les variables recueillies comprenaient les données démographiques des patients, l'utilisation d'ATX et la fréquence et le volume des transfusions d'érythrocytes administrées au cours d'une période postopératoire de 72 heures. La séance de rétroaction facilitée a porté sur les conclusions du rapport et s'est concentrée sur les facteurs contribuant aux habitudes de pratique locales et aux possibilités de changement. RéSULTATS: L'utilisation d'acide tranexamique a augmenté pour les procédures d'ATH au site d'intervention, passant de 66,6 % à 74,4 % (variation absolue, 7,9 %; intervalle de confiance [IC] à 95 %, 2,4 à 13,3). De même, l'utilisation d'ATX pour les procédures d'ATG est passée de 62,4 % à 82,3 % (variation absolue, 19,9 %; IC 95 %, 15,0 à 25,0). CONCLUSION: Les médecins et leurs équipes ont pu passer en revue leurs données de pratique sur l'utilisation d'ATX, réfléchir aux différences par rapport aux lignes directrices fondées sur des données probantes, discuter des résultats avec leurs pairs et identifier les possibilités d'amélioration. L'intervention a augmenté l'utilisation d'ATX pour l'ATG et l'ATH et a modifié la posologie pour mieux s'aligner sur les lignes directrices de pratique fondées sur des données probantes.

Destabilizing polymorphism in cervid prion protein hydrophobic core determines prion conformation and conversion efficiency.

Prion diseases are infectious neurodegenerative disorders of humans and animals caused by misfolded forms of the cellular prion protein PrPC. Prions cause disease by converting PrPC into aggregation-prone PrPSc. Chronic wasting disease (CWD) is the most contagious prion disease with substantial lateral transmission, affecting free-ranging and farmed cervids. Although the PrP primary structure is highly conserved among cervids, the disease phenotype can be modulated by species-specific polymorphisms in the prion protein gene. How the resulting amino-acid substitutions impact PrPC and PrPSc structure and propagation is poorly understood. We investigated the effects of the cervid 116A>G substitution, located in the most conserved PrP domain, on PrPC structure and conversion and on 116AG-prion conformation and infectivity. Molecular dynamics simulations revealed structural de-stabilization of 116G-PrP, which enhanced its in vitro conversion efficiency when used as recombinant PrP substrate in real-time quaking-induced conversion (RT-QuIC). We demonstrate that 116AG-prions are conformationally less stable, show lower activity as a seed in RT-QuIC and exhibit reduced infectivity in vitro and in vivo. Infectivity of 116AG-prions was significantly enhanced upon secondary passage in mice, yet conformational features were retained. These findings indicate that structurally de-stabilized PrPC is readily convertible by cervid prions of different genetic background and results in a prion conformation adaptable to cervid wild-type PrP. Conformation is an important criterion when assessing transmission barrier, and conformational variants can target a different host range. Therefore, a thorough analysis of CWD isolates and re-assessment of species-barriers is important in order to fully exclude a zoonotic potential of CWD.

Assessment of neutralizing and non-neutralizing antibody responses against Porcine circovirus 2 in vaccinated and non-vaccinated farmed pigs.

Vaccination is the most efficacious procedure to curtail Porcine circovirus 2 (PCV2)-associated diseases (PCVAD). Experimental studies indicate that PCV2 vaccine-induced virus-neutralizing antibodies play a major role in protection from PCVAD. However, the immune response to PCV2 vaccination of pigs on farms is less clear. Analysing groups of age-matched vaccinated and non-vaccinated farmed pigs, we found significantly increased levels of virus-neutralizing antibodies only in vaccinated pigs belonging to the age group with the highest risk for developing PCVAD. Serum levels of PCV2 genomes were not different between corresponding age groups. Levels of antibodies directed against a linear peptide from the PCV2 capsid protein correlated with those of virus-neutralizing antibodies and reached the highest levels in older, non-vaccinated animals, pointing towards an intense interaction between PCV2-infected cells and the immune system. In conclusion, current PCV2 vaccines are in need of improvement to induce stronger and more rapid immunity to prevent PCV2 infection.

COVID-19 outbreak among physicians at a Canadian curling bonspiel: a descriptive observational study.

BACKGROUND: Transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is known to occur among individuals who congregate in large groups, especially during indoor activities. Our objective was to provide a detailed clinical description of an outbreak of coronavirus disease 2019 (COVID-19) that occurred after a sporting and social event during the early days of the pandemic. METHODS: We conducted a descriptive study of a curling bonspiel in Edmonton held on Mar. 11-14, 2020. We used standardized interviews between Apr. 17 and May 5, 2020, to collect demographic data, travel history, symptoms (type, onset and duration), self-reported testing results for SARS-CoV-2 ribonucleic acid (RNA) using reverse transcription polymerase chain reaction (RT-PCR), and clinical outcomes. We also obtained results of convalescent SARS-CoV-2 immunoglobulin G serology. RESULTS: All 73 curlers (55 active health care workers) who participated in the bonspiel were interviewed for the study. Convalescent SARS-CoV-2 immunoglobulin G serology was completed in 62 (85%) participants. Of the 73 participants (55 [75%] male, median age 51 [range 26-79] yr, 58 [79%] physicians), 40 curlers (55%) tested positive for SARS-CoV-2 RNA by RT-PCR; an additional 16 participants developed symptoms but had negative swabs or were not tested (14 were probable cases), for a 74% attack rate (confirmed or probable cases). Anosmia with ageusia or dysgeusia occurred in 39 of 54 (72%) confirmed or probable cases. The clinical course was mild in most participants (1 emergency visit, no hospital admissions). Transmission likely occurred from multiple individuals with minor nonspecific symptoms during the event, possibly during shared meals. INTERPRETATION: The 74% attack rate (confirmed or probable cases) highlights the infectivity of SARS-CoV-2 during sporting and social events. This reinforces the need for public health measures (masking, physical distancing and limiting the size of social gatherings) during future waves of COVID-19 in Canada.

Disrupted Neurogenesis in Germ-Free Mice: Effects of Age and Sex.

The gut microbiome has profound effects on development and function of the nervous system. Recent evidence indicates that disruption of the gut microbiome leads to altered hippocampal neurogenesis. Here, we examined whether the effects of gut microbiome disruption on neurogenesis are age-dependent, given that both neurogenesis and the microbiome show age-related changes. Additionally, we examined memory induced functional connectivity of hippocampal networks. Control and germ-free mice at three different ages (4, 8, and 12 weeks) were trained in contextual fear-conditioning, then subsequently tested the following day. Hippocampal neurogenesis, quantified via BrdU and doublecortin, exhibited age-dependent changes relative to controls, with the established age-dependent decrease in neurogenesis being delayed in germ-free mice. Moreover, we found sex-dependent effects of germ-free status on neurogenesis, with 4 week old male germ-free mice having decreased neurogenesis and 8 week old female germ-free mice having increased neurogenesis. To assess systems-level consequences of disrupted neurogenesis, we assessed functional connectivity of hippocampal networks by inducing c-Fos expression with contextual memory retrieval and applying a previously described network analysis. Our results indicate impaired connectivity of the dentate gyrus in germ-free mice in a pattern highly correlated with adult neurogenesis. In control but not germ-free mice, functional connectivity became more refined with age, indicating that age dependent network refinement is disrupted in germ-free mice. Overall, the results show that disruption of the gut microbiome affects hippocampal neurogenesis in an age- and sex-dependent manner and that these changes are also related to changes in the dentate gyrus functional network.

Prion infection impairs lysosomal degradation capacity by interfering with rab7 membrane attachment in neuronal cells.

Prions are proteinaceous infectious particles which cause fatal neurodegenerative disorders in humans and animals. They consist of a mostly ß-sheeted aggregated isoform (PrP(Sc)) of the cellular prion protein (PrP(c)). Prions replicate autocatalytically in neurons and other cell types by inducing conformational conversion of PrP(c) into PrP(Sc). Within neurons, PrP(Sc) accumulates at the plasma membrane and in vesicles of the endocytic pathway. To better understand the mechanisms underlying neuronal dysfunction and death it is critical to know the impact of PrP(Sc) accumulation on cellular pathways. We have investigated the effects of prion infection on endo-lysosomal transport. Our study demonstrates that prion infection interferes with rab7 membrane association. Consequently, lysosomal maturation and degradation are impaired. Our findings indicate a mechanism induced by prion infection that supports stable prion replication. We suggest modulation of endo-lysosomal vesicle trafficking and enhancement of lysosomal maturation as novel targets for the treatment of prion diseases.

Rapid detection of neutralizing antibodies against bovine viral diarrhoea virus using quantitative high-content screening.

Bovine viral diarrhoea virus (BVDV) is an important cause of morbidity, mortality and economic losses in cattle worldwide. Humoral immunity to BVDV plays a major role in the protection against infection and disease. In vitro serum neutralization tests can quantify humoral responses, but standard protocols are time-consuming and labour-intensive. The objective of this study was to develop a highly sensitive assay based on high-content cell-by-cell screening that is faster and less subjective than the conventional protocols. It can detect a neutralizing antibody response within the first week after infection of an animal, takes less than 24h to complete and excludes operator bias by automated data acquisition and analysis.