Prediction model to identify infectious COVID-19 patients in the emergency department.

Background: Real-time reverse-transcriptase polymerase chain reaction (RT-PCR) has been the gold standard for diagnosing coronavirus disease 2019 (COVID-19) but has a lag time for the results. An effective prediction algorithm for infectious COVID-19, utilized at the emergency department (ED), may reduce the risk of healthcare-associated COVID-19. Objective: To develop a prototypic prediction model for infectious COVID-19 at the time of presentation to the ED. Material and methods: Retrospective cohort study of all adult patients admitted to Singapore General Hospital (SGH) through ED between March 15, 2020, and December 31, 2022, with admission of COVID-19 RT-PCR results. Two prediction models were developed and evaluated using area under the curve (AUC) of receiver operating characteristics (ROC) to identify infectious COVID-19 patients (cycle threshold (Ct) of <25). Results: Total of 78,687 patients were admitted to SGH through ED during study period. 6,132 of them tested severe acute respiratory coronavirus 2 positive on RT-PCR. Nearly 70% (4,226 of 6,132) of the patients had infectious COVID-19 (Ct<25). Model that included demographics, clinical history, symptom and laboratory variables had AUROC of 0.85 with sensitivity and specificity of 80.0% & 72.1% respectively. When antigen rapid test results at ED were available and added to the model for a subset of the study population, AUROC reached 0.97 with sensitivity and specificity of 95.0% and 92.8% respectively. Both models maintained respective sensitivity and specificity results when applied to validation data. Conclusion: Clinical predictive models based on available information at ED can be utilized for identification of infectious COVID-19 patients and may enhance infection prevention efforts.

Invited review: From heat stress to disease-Immune response and candidate genes involved in cattle thermotolerance.

Heat stress implies unfavorable effects on primary and functional traits in dairy cattle and, in consequence, on the profitability of the whole production system. The increasing number of days with extreme hot temperatures suggests that it is imperative to detect the heat stress status of animals based on adequate measures. However, confirming the heat stress status of an individual is still challenging, and, in consequence, the identification of novel heat stress biomarkers, including molecular biomarkers, remains a very relevant issue. Currently, it is known that heat stress seems to have unfavorable effects on immune system mechanisms, but this information is of limited use in the context of heat stress phenotyping. In addition, there is a lack of knowledge addressing the molecular mechanisms linking the relevant genes to the observed phenotype. In this review, we explored the potential molecular mechanisms explaining how heat stress affects the immune system and, therefore, increases the occurrence of immune-related diseases in cattle. In this regard, 2 relatively opposite hypotheses are under focus: the immunosuppressive action of cortisol, and the proinflammatory effect of heat stress. In both hypotheses, the modulation of the immune response during heat stress is highlighted. Moreover, it is possible to link candidate genes to these potential mechanisms. In this context, immune markers are very valuable indicators for the detection of heat stress in dairy cattle, broadening the portfolio of potential biomarkers for heat stress.

A multi-centre retrospective study of Nocardia speciation and antimicrobial susceptibility in Queensland, Australia.

The study aims to characterise the species identification and antimicrobial susceptibility testing (AST) results of Nocardial isolates from adult patients across major public hospitals in Queensland, Australia, over a 15-year period. A multi-centre retrospective observational study of Nocardia sp. isolates was conducted from 7 major public hospitals in Queensland, Australia, over a 15-year period. Clinical samples from patients aged ≥ 18 years that isolated Nocardia sp. were included. Demographic and clinical data were collected, along with species identification and AST results. Overall, 484 Nocardia sp. were isolated. Most patients were male (297, 61%) with a mean (IQR) age of 60 (51-75) and a median (IQR) Charlson Comorbidity Index of 4 (2-6). Of these, 239 (49%) patients were immunosuppressed. Organisms were most frequently isolated from sputum (174, 36%), and superficial swabs (102, 21%). Patients presented with pulmonary infections (165, 35%) and superficial skin and soft tissue infections (87, 18%) most commonly. One hundred (21%) isolates were deemed pulmonary colonisation and were not treated. Of the speciated organisms, N. nova complex was the most common (93, 19%), followed by N. farcinica complex (79, 16%). Organisms were reliably susceptible to linezolid (240/245, 98%), amikacin (455/470, 97%), and trimethoprim/sulfamethoxazole (459/476, 96%), but less so to imipenem (243/472, 51%) and ceftriaxone (261/448, 58%). This is the largest Australian description of Nocardia sp. to date. Given antimicrobials are often commenced prior to AST results and sometimes even speciation, characterisation of local species and antibiogram data is important to guide empiric choices and local guidelines.

Four cases of acute comitant esotropia associated with diffuse intrinsic pontine glioma in children.

BACKGROUND: Acute acquired concomitant esotropia (AACE) is usually a benign form of strabismus that infrequently is associated with intracranial pathology. Clinicians have noted an increase in its incidence and theorize that it may be related to public health "lockdown" measures taken in response to the COVID-19 pandemic. With an increased incidence of AACE clinicians must firstly differentiate AACE from common accommodative esotropia and secondly recognize AACE as a possible sign of serious neuropathology.Diffuse Intrinsic Pontine Glioma (DIPG) is a devastating diagnosis for affected families. Children typically present at age 6-7 years with cranial nerve palsies, long tract signs, and/or cerebellar signs. Diagnosis is made from characteristic findings on magnetic resonance brain imaging (MRI brain) and treatment includes radiotherapy and palliative care. Two years from diagnosis, 90% of affected children will have died from their disease. CASE SERIES: We present four cases that attended our pediatric ophthalmology clinic with AACE either as a presenting sign of DIPG or as a clinical finding following a DIPG diagnosis. Patient A (age 5 years) presented to the emergency eye clinic with sudden onset diplopia and intermittent esotropia. Suppression later developed, they had 0.00 logMAR visual acuity either eye, and bilateral physiological hypermetropia. MRI brain imaging requested as a result of the unusual presentation led to the DIPG diagnosis. The other 3 cases (ages 11, 5 & 5 years) were assessed post DIPG diagnosis and found to have an esotropia measuring bigger on 1/3-meter fixation than 6-meter fixation, full ocular motility, physiological hypermetropia or emmetropia, and visual acuity normal for age. Other than patient B (age 11 years), who had papilledema and gaze evoked nystagmus when they were assessed 2 weeks prior to death, no patient had any other clinical eye findings. CONCLUSIONS: This small series of 4 patients attending our clinic within a 12-month period supports the notion that children presenting with AACE should routinely be offered brain MRI. Not all children with DIPG-associated AACE have significant ophthalmic findings indicative of intracranial pathology. With the potential for increased incidence of AACE related to lockdowns, clinicians should be reminded of the infrequent possibility their patient has a more serious condition.

Actin cytoskeleton remodeling primes RIG-I-like receptor activation.

The current dogma of RNA-mediated innate immunity is that sensing of immunostimulatory RNA ligands is sufficient for the activation of intracellular sensors and induction of interferon (IFN) responses. Here, we report that actin cytoskeleton disturbance primes RIG-I-like receptor (RLR) activation. Actin cytoskeleton rearrangement induced by virus infection or commonly used reagents to intracellularly deliver RNA triggers the relocalization of PPP1R12C, a regulatory subunit of the protein phosphatase-1 (PP1), from filamentous actin to cytoplasmic RLRs. This allows dephosphorylation-mediated RLR priming and, together with the RNA agonist, induces effective RLR downstream signaling. Genetic ablation of PPP1R12C impairs antiviral responses and enhances susceptibility to infection with several RNA viruses including SARS-CoV-2, influenza virus, picornavirus, and vesicular stomatitis virus. Our work identifies actin cytoskeleton disturbance as a priming signal for RLR-mediated innate immunity, which may open avenues for antiviral or adjuvant design.

Long-term Mortality, Readmission, and Resource Utilization Among Hospital Survivors of Out-of-Hospital Cardiac Arrest.

BACKGROUND: Among patients with out-of-hospital cardiac arrest (OHCA), the influence of pre- and in-hospital factors on long-term survival, readmission, and resource utilization is ill-defined, mainly related to challenges combining disparate data sources. METHODS: Adult nontraumatic OHCA from the British Columbia Cardiac Arrest Registry (January 2009 to December 2016) were linked to provincial datasets comprising comorbidities, medications, cardiac procedures, mortality, and hospital admission and discharge. Among hospital-discharge survivors, the 3-year end point of mortality or mortality and all-cause readmission was examined with the use of the Kaplan-Meier method and multivariable Cox regression model for predictors. The use of publicly funded home care and community services within 1 year after discharge also was evaluated. RESULTS: Of the 10,674 linked, emergency medical services-treated adult OHCAs, 3230 were admitted to hospital and 1325 survived to hospital discharge. At 3 years after discharge, the estimated Kaplan-Meier survival rate was 84.1% (95% CI 81.7%-86.1%) and freedom from death or all-cause readmission was 31.8% (29.0%-34.7%). After exclusions, 26.6% (n = 315/1186) accessed residential or home care services within 1 year. Independent predictors of long-term outcomes included age and comorbidities, but also favourable arrest characteristics and in-hospital factors such as revascularization or receipt of an intracardiac defibrillator before discharge. CONCLUSIONS: Among OHCA hospital survivors, the long-term death or readmission risk persists and is modulated by both pre- and in-hospital factors. However, only 1 in 4 survivors required residential or home care after discharge. These results support efforts to improve care processes to increase survival to hospital discharge.

Safety of the use of gold nanoparticles conjugated with proinsulin peptide and administered by hollow microneedles as an immunotherapy in type 1 diabetes.

Antigen-specific immunotherapy is an immunomodulatory strategy for autoimmune diseases, such as type 1 diabetes, in which patients are treated with autoantigens to promote immune tolerance, stop autoimmune ß-cell destruction and prevent permanent dependence on exogenous insulin. In this study, human proinsulin peptide C19-A3 (known for its positive safety profile) was conjugated to ultrasmall gold nanoparticles (GNPs), an attractive drug delivery platform due to the potential anti-inflammatory properties of gold. We hypothesised that microneedle intradermal delivery of C19-A3 GNP may improve peptide pharmacokinetics and induce tolerogenic immunomodulation and proceeded to evaluate its safety and feasibility in a first-in-human trial. Allowing for the limitation of the small number of participants, intradermal administration of C19-A3 GNP appears safe and well tolerated in participants with type 1 diabetes. The associated prolonged skin retention of C19-A3 GNP after intradermal administration offers a number of possibilities to enhance its tolerogenic potential, which should be explored in future studies.

Biocompatible Supramolecular Mesoporous Silica Nanoparticles as the Next-Generation Drug Delivery System.

Supramolecular mesoporous silica nanoparticles (MSNs) offer distinct properties as opposed to micron-sized silica particles in terms of their crystal structure, morphology-porosity, toxicity, biological effects, and others. MSN biocompatibility has touched the pharmaceutical realm to exploit its robust synthesis pathway for delivery of various therapeutic molecules including macromolecules and small-molecule drugs. This article provides a brief review of MSN history followed by special emphasis on the influencing factors affecting morphology-porosity characteristics. Its applications as the next-generation drug delivery system (NGDDS) particularly in a controlled release dosage form via an oral drug delivery system are also presented and shall be highlighted as oral delivery is the most convenient route of drug administration with the economical cost of development through to scale-up for clinical trials and market launch.

Genotyping and evaluation of interleukin-10 and soluble HLA-G in abortion due to toxoplasmosis and HSV-2 infections.

Abortion is a condition that occurs due to one of the pathological injuries, often one of the members of the TORCH is the real cause. The current study aimed to investigate the impact of toxoplasmosis, HSV-2 infections with abortion, and also, the identification of immunogenetics marker (interleukin-10) that may be associated with abortion. Anti-Toxoplasma IgG, IgM, Herpes simplex virus-2 IgM, human soluble leukocyte antigen class I-G and interleukin-10 were estimated by ELISA technique, while the expression of IL-10 gene was investigated by using the real-time PCR. The results showed that among aborted women the rate of anti-Toxoplasma and HSV-2 IgM antibodies occurred within the age groups (21-30) years and (31-40) years 32(100.0%) and 36(100.0% ), respectively. A significant relationship was found between IL-10 and cases with a P=0.005. The pattern of distribution of HLA-G in the studied groups showed that there was a significant relationship between HLA-G and cases with a P=0.005. Regarding the IL-10 rs gene, the results revealed an amplified product of 377 bp and there was a high Ct value for patients and controls with a high Ct value of templates, preoperational to the gene concentration. We concluded that there was a significant relationship between human leukocyte antigen-G and the cases. It was found that there was a high Ct value for patients and controls with a high Ct value for templates.

Gastrointestinal nematode and Eimeria spp. infections in dairy cattle along a rural-urban gradient.

Endoparasite infections can lead to considerable economic losses in dairy cattle due to decreases in milk yield and quality. Environmental and host-related factors contribute to endoparasite infection intensity and probability. Moreover, advancing urbanization influences parasite infection dynamics in livestock due to close human-animal cohabitation and changes in animal housing conditions. The aim of the present study was to investigate social-ecological effects on gastrointestinal nematode (GIN) and Eimeria spp. infections in dairy cattle along a rural-urban gradient in the emerging Indian megacity Bangalore. In this regard, 726 faecal samples from 441 dairy cattle of different ages and physiological stages were collected from 101 farms and examined at three visits between June 2017 and April 2018. Based on a survey stratification index (SSI) comprising built-up density and distance to the city center, we assigned the farms to urban, mixed and rural areas. GIN eggs were identified in the faeces of 243 cattle (33.5%; 95% confidence interval [CI]: 30.1-36.9%), and Eimeria spp. oocysts in the faeces of 151 cattle (20.8%; 95% CI: 17.9-23.7%). Co-infection rates of GIN and Eimeria spp. were 8.5 to 12.2% higher in rural compared to urban and mixed areas. The SSI effect significantly influenced Eimeria spp. infection probability and oocyst per gram of faeces (OpG; P < 0.001) with an infection probability and OpG higher than 26% and 40% for cattle kept in rural areas compared to cattle from urban areas. However, the SSI effect was not significant for the infection probability of GIN and for GIN eggs per gram of faeces (EpG). Infection probabilities and EpG/OpG were significantly higher in calves and heifers compared to lactating and dry cows. Moreover, we estimated significantly lower OpG values in summer compared to the other seasons. No differences were estimated for GIN and Eimeria spp. infection probabilities and EpG/OpG with regard to pasture access and breed. The variations in endoparasite infection intensity and probability observed along the rural-urban gradient of Bangalore reflect the variability in dairy husbandry systems governed by the social-ecological context.

Drug product dispensing and estimates of use in a general population survey as a signal detection problem.

PURPOSE: Understanding potential bias due to rarity of the outcome is important when monitoring newly approved drugs and drugs with low availability to the general public. Although there is an increasing use of online surveys to investigate health outcomes, the limits of inference due to drug availability have not been studied. The goal of this study was to quantify the relationship between dispensing of prescription drugs and estimates of use in an online general population survey. METHODS: An online repeated, cross-sectional survey from 2018 to 2020 was used to estimate the number of adults in the United States who used prescription drugs in the general population and compared to estimated number of prescriptions dispensed over an equivalent time period. Joinpoint regression was used to quantify thresholds. A sample of respondents was retested to estimate reliability statistics. RESULTS: A model with a single threshold was the best fit, with the estimated threshold of 565 000 (95% CI: 9500-11 600 000) prescriptions dispensed per year. Above the threshold, there was a significant association between dispensing and estimates (p < 0.001); below the threshold, the relationship was not significant (p = 0.912). Above the threshold, responses were more reliable than random chance, and reliability steadily increased with increased dispensing. CONCLUSIONS: These results suggest the threshold demarcates two distinct pharmacoepidemiological paradigms when investigating drug use in general population surveys. Dispensing can be used as a guide to determine the epidemiological paradigm that is best suited.

Understanding Incoming Canadian and US Veterinary Students' Attitudes and Perceptions of Their Dietary Habits and Levels of Physical Activity.

As critical components of individual well-being, nutrition and physical activity have important physical and psychological implications. Veterinary students face demanding schedules and potentially high rates of psychological distress. Though veterinary students' strategies for healthy eating have been explored, factors influencing their ability to achieve a healthy diet are less understood. This study assesses incoming veterinary students' perceived attitudes to their dietary habits and physical activity levels. Incoming students (n = 322) at five Canadian and five randomly selected US veterinary schools completed a questionnaire inquiring about demographic information, dietary attitudes and habits, and activity levels. More than half (58%) of students perceived their diet to be moderately healthy. A desire to feel better and have more energy was the most reported (79%) motivating factor to modifying personal eating habits and was significantly associated with improved odds of having a perceived healthy diet (OR = 2.22, p < .024). A busy lifestyle was perceived as a barrier to changing current eating habits by 92% of respondents. Students reporting a desire to maintain their health (OR = 3.42, p < .001) and moderate (OR = 2.81, p < .003) or high (OR = 2.30, p < .044) routine physical activity levels were also more likely to perceive their diet as healthy. Findings show that incoming veterinary students' perceptions may influence their goals of achieving a healthy lifestyle. An understanding of incoming veterinary students' barriers and motivators could be applied in future research to assist students in achieving personalized goals.

Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses.

Nucleic acids are used in many therapeutic modalities, including gene therapy, but their ability to trigger host immune responses in vivo can lead to decreased safety and efficacy. In the case of adeno-associated viral (AAV) vectors, studies have shown that the genome of the vector activates Toll-like receptor 9 (TLR9), a pattern recognition receptor that senses foreign DNA. Here, we engineered AAV vectors to be intrinsically less immunogenic by incorporating short DNA oligonucleotides that antagonize TLR9 activation directly into the vector genome. The engineered vectors elicited markedly reduced innate immune and T cell responses and enhanced gene expression in clinically relevant mouse and pig models across different tissues, including liver, muscle, and retina. Subretinal administration of higher-dose AAV in pigs resulted in photoreceptor pathology with microglia and T cell infiltration. These adverse findings were avoided in the contralateral eyes of the same animals that were injected with the engineered vectors. However, intravitreal injection of higher-dose AAV in macaques, a more immunogenic route of administration, showed that the engineered vector delayed but did not prevent clinical uveitis, suggesting that other immune factors in addition to TLR9 may contribute to intraocular inflammation in this model. Our results demonstrate that linking specific immunomodulatory noncoding sequences to much longer therapeutic nucleic acids can "cloak" the vector from inducing unwanted immune responses in multiple, but not all, models. This "coupled immunomodulation" strategy may widen the therapeutic window for AAV therapies as well as other DNA-based gene transfer methods.

Proofs for genotype by environment interactions considering pedigree and genomic data from organic and conventional cow reference populations.

The aim of the present study was to prove genotype by environment interactions (G × E) for production, longevity, and health traits considering conventional and organic German Holstein dairy cattle subpopulations. The full data set included 141,778 Holstein cows from 57 conventional herds and 7,915 cows from 9 organic herds. The analyzed traits were first-lactation milk yield and fat percentage (FP), the length of productive life (LPL) and the health traits mastitis, ovarian cycle disorders, and digital dermatitis in first lactation. A subset of phenotyped cows was genotyped and used for the implementation of separate cow reference populations. After SNP quality controls, the cow reference sets considered 40,830 SNP from 19,700 conventional cows and the same 40,830 SNP from 1,282 organic cows. The proof of possible G × E was made via multiple-trait model applications, considering same traits from the conventional and organic population as different traits. In this regard, pedigree (A), genomic (G) and combined relationship (H) matrices were constructed. For the production traits, heritabilities were very similar in both organic and conventional populations (i.e., close to 0.70 for FP and close to 0.40 for milk yield). For low heritability health traits and LPL, stronger heritability fluctuations were observed, especially for digital dermatitis with 0.05 ± 0.01 (organic, A matrix) to 0.33 ± 0.04 (conventional, G matrix). Quite large genetic correlations between same traits from the 2 environments were estimated for production traits, especially for high heritability FP. For LPL, the genetic correlation was 0.67 (A matrix) and 0.66 (H matrix). The genetic correlation between LPL organic with LPL conventional was 0.94 when considering the G matrix, but only 213 genotyped cows were included. For health traits, genetic correlations were throughout lower than 0.80, indicating possible G × E. Genetic correlations from the different matrices A, G, and H for health and production traits followed the same pattern, but the estimates from G for health traits were associated with quite large standard errors. In genome-wide association studies, significantly associated SNP for production traits overlapped in the conventional and organic population. In contrast, for low heritability LPL and health traits, significantly associated SNP and annotated potential candidate genes differed in both populations. In this regard, significantly associated SNP for mastitis from conventional cows were located on Bos taurus autosomes 6 and 19, but on Bos taurus autosomes 1, 10, and 22 in the organic population. For the remaining health traits and LPL, different potential candidate genes were annotated, but the different genes reflect similar physiological pathways. We found evidence of G × E for low heritability functional traits, suggesting different breeding approaches in organic and conventional populations. Nevertheless, for a verification of results and implementation of alternative breeding strategies, it is imperative to increase the organic cow reference population.

A feasibility study for CODE-MI: High-sensitivity cardiac troponin-Optimizing the diagnosis of acute myocardial infarction/injury in women.

BACKGROUND: CODE-MI is a pan-Canadian, multicentre, stepped-wedge, cluster randomized trial that evaluates the impact of using the female-specific 99th percentile threshold for high-sensitivity cardiac troponin (hs-cTn) on the diagnosis, treatment and outcomes of women presenting to the emergency department (ED) with symptoms suggestive for myocardial ischemia. A feasibility study was conducted to estimate the number of eligible patients, the rate of the study's primary outcome under control conditions, and the statistical power to detect a clinically important difference in the primary outcome. METHODS: Using linked administrative data from 11 hospitals in Ontario, Canada, from October 2014 to September 2017, the following estimates were obtained: number of women presenting to the ED with symptoms suggestive of myocardial ischemia and a 24-hour peak hs-cTn value within the female-specific and overall thresholds (ie, primary cohort); the rate of the 1-year composite outcome of all-cause mortality, re-admission for nonfatal myocardial infarction, incident heart failure, or emergent/urgent coronary revascularization. Study power was evaluated via simulations. RESULTS: Overall, 2,073,849 ED visits were assessed. Among women, chest pain (with or without cardiac features) and shortness of breath were the most common complaints associated with a diagnosis of acute coronary syndrome. An estimated 7.7% of women with these complaints are eligible for inclusion in the primary cohort. The rate of the 1-year outcome in the primary cohort varied significantly across hospitals with a median rate of 12.2% (95%CI: 7.9%-17.7%). With 30 hospitals, randomized at 5-month intervals in 5 steps, approximately 19,600 women are expected to be included in CODE-MI, resulting in >82% power to detect a 20% decrease in the odds of the primary outcome at a 0.05 significance level. CONCLUSIONS: This feasibility study greatly enhanced the design of CODE-MI, allowed accurate evaluation of the study power, and demonstrated the strength of using linked administrative health data to guide the design of pragmatic clinical trials.

Ontario Veterinary College First-Year Veterinary Students' Perceptions of Companion Animal Nutrition and Their Own Nutrition: Implications for a Veterinary Nutrition Curriculum.

Extant research shows veterinarians face increasing challenges in discussing nutrition with clients despite receiving professional nutrition education in the veterinary medical curriculum. This article's aim is to elicit student veterinarians' baseline nutrition-related perceptions and nutrition information-seeking behaviors at the time of entering veterinary school. Participants were newly enrolled veterinary students at the Ontario Veterinary College (n = 120). Focus group discussions (n = 19) informed the design of an online questionnaire capturing students' demographics and perceptions of their own and their pets' nutrition. Students reported being influenced by individual factors (e.g., time), social networks (e.g., family), and surrounding environment (e.g., cost, contradictory media messages). Overall, 58% of students considered themselves knowledgeable about pet nutrition when commencing veterinary school, with 71% prioritizing their pets' diets as much as their own. Students' confidence in finding pet nutrition information was correlated with perceived accessibility (r = .76, p = .001) and perceived quantity of information available on pet nutrition (r = .83, p = .001), but not quality of information (r = .13, p = .03). In general, students relied on and trusted veterinarians for nutrition advice. However, 94% of students mistrusted pet food companies' motivations. Our data support that students entering veterinary school have their own perceptions on pet nutrition that impact nutrition education, suggesting this as an important consideration in the design and delivery of a veterinary nutrition curriculum. Veterinary medical faculty should be encouraged to discuss baseline nutrition information and address any misconceptions to prepare students for future consultations with clients.

Anticoagulation for Patients With Atrial Fibrillation and End-Stage Renal Disease on Dialysis: A National Survey.

Patients with atrial fibrillation (AF) have a significant increased risk of embolic stroke. Patients with end-stage renal disease who are on dialysis have an increased risk of both embolic stroke and bleeding. Stroke-prevention studies with the use of anticoagulation for AF patients have excluded patients on dialysis, so there remains no consensus on their management. We developed and implemented a pan-Canadian multidisciplinary survey to explore the current beliefs and practices concerning patients with AF on dialysis. We developed an online investigator-designed survey with both quantitative and qualitative responses with the use of a secure university-affiliated electronic service. The survey was distributed to physicians via the QxMD platform and directly to internal medicine, cardiology, and nephrology residency program directors for distribution to faculty members. 130 participants responded, including 46 cardiologists, 45 nephrologists, 30 general internists, and 9 other physicians. The preferred anticoagulant was warfarin. The CHADS2 score used to initiate anticoagulation was highly variable, with specialties differing in use of a CHADS2 threshold of ≥ 1 (P < 0.001) and the impact of previous transient ischemic attack/stroke (P = 0.02). Calciphylaxis history affected the decision to prescribe anticoagulation. Specialties differed in thresholds used to consider direct oral anticoagulants for dialysis patients, with nephrologists more likely to prescribe anticoagulation at higher CHADS2 scores. Our survey demonstrated significant heterogeneity of anticoagulation use for stroke prevention in patients with AF on dialysis. Physician specialty and patient risk profiles contributed to the observed variability. This study reemphasises the need for clinical trials, large observational studies, and consensus guidelines to address evident equipoise.

Trends in Imaging for Suspected Pulmonary Embolism Across US Health Care Systems, 2004 to 2016.

Importance: In response to calls to reduce unnecessary diagnostic testing with computed tomographic pulmonary angiography (CTPA) for suspected pulmonary embolism (PE), there have been growing efforts to create and implement decision rules for PE testing. It is unclear if the use of advanced imaging tests for PE has diminished over time. Objective: To assess the use of advanced imaging tests, including chest computed tomography (CT) (ie, all chest CT except for CTPA), CTPA, and ventilation-perfusion (V/Q) scan, for PE from 2004 to 2016. Design, Setting, and Participants: Cohort study of adults by age group (18-64 years and ≥65 years) enrolled in 7 US integrated and mixed-model health care systems. Joinpoint regression analysis was used to identify years with statistically significant changes in imaging rates and to calculate average annual percentage change (growth) from 2004 to 2007, 2008 to 2011, and 2012 to 2016. Analyses were conducted between June 11, 2019, and March 18, 2020. Main Outcomes and Measures: Rates of chest CT, CTPA, and V/Q scan by year and age, as well as annual change in rates over time. Results: Overall, 3.6 to 4.8 million enrollees were included each year of the study, for a total of 52 343 517 person-years of follow-up data. Adults aged 18 to 64 years accounted for 42 223 712 person-years (80.7%) and those 65 years or older accounted for 10 119 805 person-years (19.3%). Female enrollees accounted for 27 712 571 person-years (52.9%). From 2004 and 2016, chest CT use increased by 66.3% (average annual growth, 4.4% per year), CTPA use increased by 450.0% (average annual growth, 16.3% per year), and V/Q scan use decreased by 47.1% (decreasing by 4.9% per year). The use of CTPA increased most rapidly from 2004 to 2006 (44.6% in those aged 18-64 years and 43.9% in those ≥65 years), with ongoing rapid growth from 2006 to 2010 (annual growth, 19.8% in those aged 18-64 years and 18.3% in those ≥65 years) and persistent but slower growth in the most recent years (annual growth, 4.3% in those aged 18-64 years and 3.0% in those ≥65 years from 2010 to 2016). The use of V/Q scanning decreased steadily since 2004. Conclusions and Relevance: From 2004 to 2016, rates of chest CT and CTPA for suspected PE continued to increase among adults but at a slower pace in more contemporary years. Efforts to combat overuse have not been completely successful as reflected by ongoing growth, rather than decline, of chest CT use. Whether the observed imaging use was appropriate or was associated with improved patient outcomes is unknown.