Rady Faculty of Health Sciences Scholarly Works

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Open Access
1072. Red blood cell transfusion in acute cerebral injuries: a systematic review of preclinical animal studies
(2014-09-26) Laflamme, M; Boutin, A; Haghbayan, H; Shemilt, M; Lauzier, F; Moore, L; Zarychanski, R; Lacroix, J; Lamontagne, F; Fergusson, DA; Desjardins, P; Turgeon, AF
Open Access
10th anniversary of allergy, asthma & clinical immunology
(2014-10-22) Warrington, Richard J; Keith, Paul K
AbstractThis is an Editorial
Open Access
2010 International consensus algorithm for the diagnosis, therapy and management of hereditary angioedema
(2010-07-28) Bowen, Tom; Cicardi, Marco; Farkas, Henriette; Bork, Konrad; Longhurst, Hilary J; Zuraw, Bruce; Aygoeren-Pursun, Emel; Craig, Timothy; Binkley, Karen; Hebert, Jacques; Ritchie, Bruce; Bouillet, Laurence; Betschel, Stephen; Cogar, Della; Dean, John; Devaraj, Ramachand; Hamed, Azza; Kamra, Palinder; Keith, Paul K; Lacuesta, Gina; Leith, Eric; Lyons, Harriet; Mace, Sean; Mako, Barbara; Neurath, Doris; Poon, Man-Chiu; Rivard, Georges-Etienne; Schellenberg, Robert; Rowan, Dereth; Rowe, Anne; Stark, Donald; Sur, Smeeksha; Tsai, Ellie; Warrington, Richard; Waserman, Susan; Ameratunga, Rohan; Bernstein, Jonathan; Bjorkander, Janne; Brosz, Kristylea; Brosz, John; Bygum, Anette; Caballero, Teresa; Frank, Mike; Fust, George; Harmat, George; Kanani, Amin; Kreuz, Wolfhart; Levi, Marcel; Li, Henry; Martinez-Saguer, Inmaculada; Moldovan, Dumitru; Nagy, Istvan; Nielsen, Erik W; Nordenfelt, Patrik; Reshef, Avner; Rusicke, Eva; Smith-Foltz, Sarah; Spath, Peter; Varga, Lilian; Xiang, Zhi Y
Abstract Background We published the Canadian 2003 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema (HAE; C1 inhibitor [C1-INH] deficiency) and updated this as Hereditary angioedema: a current state-of-the-art review: Canadian Hungarian 2007 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema. Objective To update the International Consensus Algorithm for the Diagnosis, Therapy and Management of Hereditary Angioedema (circa 2010). Methods The Canadian Hereditary Angioedema Network (CHAEN)/Réseau Canadien d'angioédème héréditaire (RCAH) http://www.haecanada.com and cosponsors University of Calgary and the Canadian Society of Allergy and Clinical Immunology (with an unrestricted educational grant from CSL Behring) held our third Conference May 15th to 16th, 2010 in Toronto Canada to update our consensus approach. The Consensus document was reviewed at the meeting and then circulated for review. Results This manuscript is the 2010 International Consensus Algorithm for the Diagnosis, Therapy and Management of Hereditary Angioedema that resulted from that conference. Conclusions Consensus approach is only an interim guide to a complex disorder such as HAE and should be replaced as soon as possible with large phase III and IV clinical trials, meta analyses, and using data base registry validation of approaches including quality of life and cost benefit analyses, followed by large head-to-head clinical trials and then evidence-based guidelines and standards for HAE disease management.
Open Access
2078- Immunotherapy – 2078: Allergen-specific oral immunotherapy for peanut allergy: a Cochrane systematic review
(2013-04-23) Nurmatov, Ulugbek; Venderbosch, Iris; Devereux, Graham; Simons, F Estelle R; Sheikh, Aziz
Open Access
2078- Immunotherapy – 2078. Allergen-specific oral immunotherapy for peanut allergy: a Cochrane systematic review
(2013-04-23) Nurmatov, Ulugbek; Venderbosch, Iris; Devereux, Graham; Simons, F E R; Sheikh, Aziz
Open Access
3D nuclear organization and genomic instability in cancer
(2013-04-04) Mai, Sabine
Open Access
7 versus 14 days of antibiotic treatment for critically ill patients with bloodstream infection: a pilot randomized clinical trial
(2018-02-17) Daneman, Nick; Rishu, Asgar H; Pinto, Ruxandra; Aslanian, Pierre; Bagshaw, Sean M; Carignan, Alex; Charbonney, Emmanuel; Coburn, Bryan; Cook, Deborah J; Detsky, Michael E; Dodek, Peter; Hall, Richard; Kumar, Anand; Lamontagne, Francois; Lauzier, Francois; Marshall, John C; Martin, Claudio M; McIntyre, Lauralyn; Muscedere, John; Reynolds, Steven; Sligl, Wendy; Stelfox, Henry T; Wilcox, M. E; Fowler, Robert A
Abstract Background Shorter-duration antibiotic treatment is sufficient for a range of bacterial infections, but has not been adequately studied for bloodstream infections. Our systematic review, survey, and observational study indicated equipoise for a trial of 7 versus 14 days of antibiotic treatment for bloodstream infections; a pilot randomized clinical trial (RCT) was a necessary next step to assess feasibility of a larger trial. Methods We conducted an open, pilot RCT of antibiotic treatment duration among critically ill patients with bloodstream infection across 11 intensive care units (ICUs). Antibiotic selection, dosing and route were at the discretion of the treating team; patients were randomized 1:1 to intervention arms consisting of two fixed durations of treatment – 7 versus 14 days. We recruited adults with a positive blood culture yielding pathogenic bacteria identified while in ICU. We excluded patients with severe immunosuppression, foci of infection with an established requirement for prolonged treatment, single cultures with potential contaminants, or cultures yielding Staphylococcus aureus or fungi. The primary feasibility outcomes were recruitment rate and adherence to treatment duration protocol. Secondary outcomes included 90-day, ICU and hospital mortality, relapse of bacteremia, lengths of stay, mechanical ventilation and vasopressor duration, antibiotic-free days, Clostridium difficile, antibiotic adverse events, and secondary infection with antimicrobial-resistant organisms. Results We successfully achieved our target sample size (n = 115) and average recruitment rate of 1 (interquartile range (IQR) 0.3–1.5) patient/ICU/month. Adherence to treatment duration was achieved in 89/115 (77%) patients. Adherence differed by underlying source of infection: 26/31 (84%) lung; 18/29 (62%) intra-abdominal; 20/26 (77%) urinary tract; 8/9 (89%) vascular-catheter; 4/4 (100%) skin/soft tissue; 2/4 (50%) other; and 11/12 (92%) unknown sources. Patients experienced a median (IQR) 14 (8–17) antibiotic-free days (of the 28 days after blood culture collection). Antimicrobial-related adverse events included hepatitis in 1 (1%) patient, Clostridium difficile infection in 4 (4%), and secondary infection with highly resistant microorganisms in 10 (9%). Ascertainment was complete for all study outcomes in ICU, in hospital and at 90 days. Conclusion It is feasible to conduct a RCT to determine whether 7 versus 14 days of antibiotic treatment is associated with comparable 90-day survival. Trial registration ClinicalTrials.gov , identifier: NCT02261506 . Registered on 26 September 2014.
Open Access
A (H1N1) pdm09 HA D222 variants associated with severity and mortality in patients during a second wave in Mexico
(2013-01-31) Vazquez-Perez, Joel A; Isa, Pavel; Kobasa, Darwyn; Ormsby, Christopher E; Ramirez-Gonzalez, Jose E; Romero-Rodriguez, Damaris P; Ranadheera, Charlene; Li, Yan; Bastien, Nathalie; Embury-Hyatt, Carissa; Gonzalez-Duran, Elizabeth; Barrera-Badillo, Gisela; Ablanedo-Terrazas, Yuria; Sevilla-Reyes, Edgar E; Escalera-Zamudio, Marina; Cobian-Guemes, Ana G; Lopez, Irma; Ortiz-Alcantara, Joanna; Alpuche-Aranda, Celia; Perez-Padilla, Jose R; Reyes-Teran, Gustavo
Abstract Background Pandemic type A (H1N1) influenza arose in early 2009, probably in Mexico and the United States, and reappeared in North America in September for seven more months. An amino acid substitution in the hemagglutinin (HA), D222G, has been reported in a significant proportion of patients with a severe and fatal outcome. We studied the prevalence of HA222 substitutions in patients in Mexico during the second wave and its association with clinical outcome and pathogenicity in a mouse model. Methods The nucleotide sequences of hemagglutinin (HA) from viruses collected from 77 patients were determined including 50 severe and fatal cases and 27 ambulatory cases. Deep sequencing was done on 5 samples from severe or fatal cases in order to determine the quasispecies proportion. Weight loss and mortality due to infection with cultured influenza viruses were analyzed in a mouse model. Results Viruses from 14 out of 50 hospitalized patients (28%) had a non aspartic acid residue at the HA 222 position (nD222), while all 27 ambulatory patients had D222 (p = 0.0014). G222 was detected as sole species or in coexistence with N222 and D222 in 12 patients with severe disease including 8 who died. N222 in coexistence with D222 was detected in 1 patient who died and co-occurrence of A222 and V222, together with D222, was detected in another patient who died. The patients with a nD222 residue had higher mortality (71.4%), compared to the group with only D222 (22.2%, p = 0.0008). Four of the 14 viruses from hospitalized patients were cultured and intranasally infected into mice. Two viruses with G222 were lethal while a third virus, with G222, caused only mild illness in mice similar to the fourth virus that contained D222. Conclusions We confirm the elevated incidence of HA222 (H1N1)pdm09 variants in severe disease and mortality. Both clinical and mouse infection data support the idea that nD222 mutations contribute to increased severity of disease but additional determinants in disease outcome may be present.
Open Access
A bioavailable form of curcumin, in combination with vitamin-D- and omega-3-enriched diet, modifies disease onset and outcomes in a murine model of collagen-induced arthritis
(2021-01-25) Hemshekhar, Mahadevappa; Anaparti, Vidyanand; El-Gabalawy, Hani; Mookherjee, Neeloffer
Abstract Objective Curcumin (CUR), vitamin D3 (D3), and omega-3-fatty acids (O3FA) individually modulate inflammation and pain in arthritis. Although these supplements are widely used, their combinatorial effects have not been defined. In this study, we examined the effects of a D3 and O3FA (VO)-enriched diet in conjunction with a highly bioavailable form of CUR (Cureit/Acumin™) in a collagen-induced arthritis (CIA) murine model. Methods Male DBA/1J mice were acclimatized to VO-enriched diet and challenged with bovine collagen II (CII). Bioavailable CUR was administered daily by oral gavage from the onset of CII challenge. Disease severity was determined by monitoring joint thickness and standardized clinical score. Cellular infiltration and cartilage degradation in the joints were assessed by histology, serum cytokines profiled by Meso Scale Discovery multiplex assay, and joint matrix metalloproteinases examined by western blots. Results CUR by itself significantly decreased disease severity by ~ 60%. Administration of CUR in CIA mice taking a VO-enriched diet decreased disease severity by > 80% and maximally delayed disease onset and progression. Some of the disease-modifying effects was mediated by CUR alone, e.g., suppression of serum anti-collagen antibodies and decrease of cellular infiltration and MMP abundance in the joints of CIA mice. Although CUR alone suppressed inflammatory cytokines in serum of CIA mice, the combination of CUR and VO diet significantly enhanced the suppression (> 2-fold compared to CUR) of TNF, IFN-γ, and MCP-1, all known to be associated with RA pathogenesis. Conclusion This study provides proof-of-concept that the combination of bioavailable CUR, vitamin D3, and O3FA substantially delays the development and severity of CIA. These findings provide a rationale for systematically evaluating these widely available supplements in individuals at risk for developing future RA.
Open Access
A birth cohort study to investigate the association between prenatal phthalate and bisphenol A exposures and fetal markers of metabolic dysfunction
(2014-10-22) Ashley-Martin, Jillian; Dodds, Linda; Arbuckle, Tye E; Ettinger, Adrienne S; Shapiro, Gabriel D; Fisher, Mandy; Morisset, Anne-Sophie; Taback, Shayne; Bouchard, Maryse F; Monnier, Patricia; Dallaire, Renee; Fraser, William D
Abstract Background Obesity and type-2 diabetes are on the rise and in utero exposure to environmental contaminants is a suspected contributing factor. Our objective was to examine associations between prenatal exposure to potential endocrine disrupting chemicals and markers of fetal metabolic dysfunction. Methods The Maternal-Infant Research on Environmental Chemicals Study (MIREC) recruited 2001 women during the first trimester of pregnancy from 10 Canadian sites. First trimester maternal urine was measured for 11 phthalate metabolites and bisphenol A (BPA). Leptin and adioponectin measured in 1,363 available umbilical cord blood samples served as markers of metabolic function. Restricted cubic spline curves were used to assess the relationship between continuous measures of phthalate and BPA levels and cord blood adipokines. Polytomous logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI) for the association between phthalates and BPA and both high (≥90th percentile) and low (≤10th percentile) fetal adiponectin and leptin, adjusting for confounding factors. Analyses were conducted for all subjects, overall, and separately by fetal sex. Results Leptin was significantly higher in female than male infants. We observed an inverse, non-linear relationship between BPA and adiponectin among males in the restricted cubic spline and linear regression analysis. Mono-(3-carboxypropyl) (MCPP) was associated with increased odds of high leptin among males in the polytomous logistic regression models (4th quartile OR = 3.5 95% CI: 1.1-11.6). Conclusion Our findings contribute to the growing body of evidence examining the influence of early life exposure on metabolic regulation and function. Associations between maternal exposure to chemicals and markers of metabolic function appear to be potentially sex specific. However, further investigation is required to determine whether in utero and childhood exposure to BPA and phthalates are associated with metabolic dysfunctions later in life.
Open Access
A Case of Acquired Rifampin Resistance in Mycobacterium bovis Bacillus Calmette-Guérin-Induced Cystitis: Necessity for Treatment Guidelines
(2006-1-1) Wolfe, Joyce N; Blackwood-Antonation, Kym S; Sharma, Meenu K; Cook, Victoria J
A case of presumed bacillus Calmette-Guérin (BCG) cystitis in an elderly female patient following direct intravesical BCG instillation treatment for papillary transitional cell carcinoma is reported. The organism cultured from urine samples was eventually identified as a rifampin-resistant Mycobacterium bovis BCG isolate. Because the patient had received rifampin monotherapy during the course of treatment for presumed BCG disease, the clinical picture favoured acquired rifampin resistance. Sequencing of the target gene for rifampin (rpoB) confirmed a known mutation responsible for conferring high levels of resistance to both rifampin and rifabutin (Ser531Tyr). To the authors' knowledge, this is the first reported case of M bovis BCG disease in a non-HIV patient where the organism had acquired drug resistance to rifampin, and the second reported case of M bovis BCG that had acquired drug resistance. The present case demonstrates the necessity to re-evaluate appropriate guidelines for the effective treatment of BCG disease.
Open Access
A Case of Group A Streptococcal Meningitis in an Adult
(1993-1-1) Pattullo, Andrew LS; Bow, Eric J
Group A streptococci are an important cause of soft tissue infections but have rarely been reported as the cause of pyogenic meningitis since the advent of antibiotics. A case of group A streptococcal meningitis in an adult is presented along with a review of similar cases reported in the literature. This case serves to illustrate the virulent nature of this pathogen in infections of the meninges, the potential for associated complications, and the need for rapid diagnosis and appropriate treatment. The source of infection in this and many other cases in the literature is the upper respiratory tract. The case presented responded well to antibiotics but resulted in permanent auditory-vestibular dysfunction.
Open Access
A Case-Control Study of the Role of Cold Symptoms and other Historical Triggering Factors in Asthma Exacerbations
(2000-1-1) Tarlo, Susan M; Broder, Irvin; Corey, Paul; Chan-Yeung, Moira; Ferguson, Alexander; Becker, Allan; Warren, Peter; Simons, F Estelle R; Sherlock, Christopher; Okada, Marilyn; Manfreda, Jure
BACKGROUND: Asthma exacerbations can be provoked by many triggers such as allergens, respiratory irritants and viral infections. The relative importance of these has not been prospectively documented in a case-control study.OBJECTIVE: To assess the relative importance of colds and other nonclimatic historical triggers of asthma exacerbations.METHODS: One hundred and nineteen adults and children with asthma in two Canadian cities participated in a one-year study of the role of exacerbating factors in asthma. Among these, 36 pairs (21 adult, 15 children) completed the case-control study. Patients were considered cases if they developed an acute asthma exacerbation and notified the centre within 24 h to allow the completion of a questionnaire and viral studies (cultures of nasopharyngeal swabs and serology). Control people with asthma were matched for sex, age and area of residence, had no exacerbation during the preceding four weeks and participated within 48 h of the case patients.RESULTS: Case patients versus control patients had a mean age of 22 years versus 20 years, 50% versus 55% were male, and 92% versus 86% had at least one positive aeroallergen skin test. Cases were more likely to have taken regular inhaled steroids (63% versus 33%, Pud_less_than0.002). Cases were more likely to report the following within the previous week: fever (Pud_less_than0.001), sore throat (Pud_less_than0.001), increase in nasal symptoms (Pud_less_than0.01), increased dust exposure (Pud_less_than0.05), exposure to others with a cold (Pud_less_than0.001) and, over the previous year, increased passive smoke exposure (Pud_less_than0.05). Viral cultures and paired serology were negative.CONCLUSIONS: Symptomatic colds were the most common trigger of asthma exacerbations in the winter and spring, while a transient increase in dust exposure was also identified as a significant trigger. The association with chronic, passive smoke exposure and the use of inhaled costicosteroid medications likely reflected less stable pre-study asthma in those with exacerbations.
Open Access
A cluster-based analysis evaluating the impact of comorbidities in fibrotic interstitial lung disease
(2020-12-07) Wong, Alyson W; Lee, Tae Y; Johannson, Kerri A; Assayag, Deborah; Morisset, Julie; Fell, Charlene D; Fisher, Jolene H; Shapera, Shane; Gershon, Andrea S; Cox, Gerard; Halayko, Andrew J; Hambly, Nathan; Manganas, Helene; Sadatsafavi, Mohsen; Wilcox, Pearce G; To, Teresa; Marcoux, Veronica; Khalil, Nasreen; Kolb, Martin; Ryerson, Christopher J
Abstract Background Comorbidities are frequent and have been associated with poor quality of life, increased hospitalizations, and mortality in patients with interstitial lung disease (ILD). However, it is unclear how comorbidities lead to these negative outcomes and whether they could influence ILD disease progression. The goal of this study was to identify clusters of patients based on similar comorbidity profiles and to determine whether these clusters were associated with rate of lung function decline and/or mortality. Methods Patients with a major fibrotic ILD (idiopathic pulmonary fibrosis (IPF), fibrotic hypersensitivity pneumonitis, connective tissue disease-associated ILD, and unclassifiable ILD) from the CAnadian REgistry for Pulmonary Fibrosis (CARE-PF) were included. Hierarchical agglomerative clustering of comorbidities, age, sex, and smoking pack-years was conducted for each ILD subtype to identify combinations of these features that frequently occurred together in patients. The association between clusters and change in lung function over time was determined using linear mixed effects modeling, with adjustment for age, sex, and smoking pack-years. Kaplan Meier curves were used to assess differences in survival between the clusters. Results Discrete clusters were identified within each fibrotic ILD. In IPF, males with obstructive sleep apnea (OSA) had more rapid decline in FVC %-predicted (− 11.9% per year [95% CI − 15.3, − 8.5]) compared to females without any comorbidities (− 8.1% per year [95% CI − 13.6, − 2.7]; p = 0.03). Females without comorbidities also had significantly longer survival compared to all other IPF clusters. There were no significant differences in rate of lung function decline or survival between clusters in the other fibrotic ILD subtypes. Conclusions The combination of male sex and OSA may portend worse outcomes in IPF. Further research is required to elucidate the interplay between sex and comorbidities in ILD, as well as the role of OSA in ILD disease progression.
Open Access
A community-based qualitative study on the experience and understandings of intimate partner violence and HIV vulnerability from the perspectives of female sex workers and male intimate partners in North Karnataka state, India
(2018-05-11) Blanchard, Andrea K; Nair, Sapna G; Bruce, Sharon G; Ramanaik, Satyanarayana; Thalinja, Raghavendra; Murthy, Srikanta; Javalkar, Prakash; Pillai, Priya; Collumbien, Martine; Heise, Lori; Isac, Shajy; Bhattacharjee, Parinita
Abstract Background Research has increasingly documented the important role that violence by clients and the police play in exacerbating HIV vulnerability for women in sex work. However few studies have examined violence in the intimate relationships of women in sex work, or drawn on community partnerships to explore the social dynamics involved. A community-based participatory research study was undertaken by community and academic partners leading intimate partner violence (IPV) and HIV prevention programs in Bagalkot district, Karnataka state, India. The purpose was to explore the experience and understandings of intimate partner violence and HIV/AIDS among women in sex work and their intimate partners in Bagalkot that would inform both theory and practice. Methods A community-based, interpretive qualitative methodology was used. Data was collected between July and October 2014 through in-depth interviews with 38 participants, including 10 couples, 13 individual female sex workers, and 5 individual male intimate partners. Purposive sampling was done to maximize variation on socio-demographic characteristics. Thematic content analysis was conducted through coding and categorization for each interview question in NVivo 10.0, followed by collaborative analysis to answer the research questions. Results The results showed that an array of interrelated, multi-level factors underlay the widespread acceptance and perpetuation of violence and lack of condom use in participants’ intimate relationships. These included individual expectations that justified violence and reflected societal gender norms, compounded by stigma, legal and economic constraints relating to sex work. The results demonstrate that structural vulnerability to IPV and HIV must be addressed not only on the individual and relationship levels to resolve relevant triggers of violence and lack of condom use, but also the societal-level to address gender norms and socio-economic constraints among women in sex work and their partners. Conclusion The study contributes to a better understanding on the interplay of individual agency and structural forces at a time when researchers and program planners are increasingly pondering how best to address complex and intersecting social and health issues. Ongoing research should assess the generalizability of the results and the effectiveness of structural interventions aiming to reduce IPV and HIV vulnerability in other contexts.
Open Access
A comparative analysis of centralized waiting lists for patients without a primary care provider implemented in six Canadian provinces: study protocol
(2017-01-21) Breton, Mylaine; Green, Michael; Kreindler, Sara; Sutherland, Jason; Jbilou, Jalila; Wong, Sabrina T; Shaw, Jay; Crooks, Valorie A; Contandriopoulos, Damien; Smithman, Mélanie A; Brousselle, Astrid
Abstract Background Having a regular primary care provider (i.e., family physician or nurse practitioner) is widely considered to be a prerequisite for obtaining healthcare that is timely, accessible, continuous, comprehensive, and well-coordinated with other parts of the healthcare system. Yet, 4.6 million Canadians, approximately 15% of Canada’s population, are unattached; that is, they do not have a regular primary care provider. To address the critical need for attachment, especially for more vulnerable patients, six Canadian provinces have implemented centralized waiting lists for unattached patients. These waiting lists centralize unattached patients’ requests for a primary care provider in a given territory and match patients with providers. From the little information we have on each province’s centralized waiting list, we know the way they work varies significantly from province to province. The main objective of this study is to compare the different models of centralized waiting lists for unattached patients implemented in six provinces of Canada to each other and to available scientific knowledge to make recommendations on ways to improve their design in an effort to increase attachment of patients to a primary care provider. Methods A logic analysis approach developed in three steps will be used. Step 1: build logic models that describe each province’s centralized waiting list through interviews with key stakeholders in each province; step 2: develop a conceptual framework, separate from the provincially informed logic models, that identifies key characteristics of centralized waiting lists for unattached patients and factors influencing their implementation through a literature review and interviews with experts; step 3: compare the logic models to the conceptual framework to make recommendations to improve centralized waiting lists in different provinces during a pan Canadian face-to-face exchange with decision-makers, clinicians and researchers. Discussion This study is based on an inter-provincial learning exchange approach where we propose to compare centralized waiting lists and analyze variations in strategies used to increase attachment to a regular primary care provider. Fostering inter-provincial healthcare systems connectivity to improve centralized waiting lists’ practices across Canada can lever attachment to a regular provider for timely access to continuous, comprehensive and coordinated healthcare for all Canadians and particular for those who are vulnerable.
Open Access
A comparative study of the gut microbiota in immune-mediated inflammatory diseases—does a common dysbiosis exist?
(2018-12-13) Forbes, Jessica D; Chen, Chih-yu; Knox, Natalie C; Marrie, Ruth-Ann; El-Gabalawy, Hani; de Kievit, Teresa; Alfa, Michelle; Bernstein, Charles N; Van Domselaar, Gary
Abstract Background Immune-mediated inflammatory disease (IMID) represents a substantial health concern. It is widely recognized that IMID patients are at a higher risk for developing secondary inflammation-related conditions. While an ambiguous etiology is common to all IMIDs, in recent years, considerable knowledge has emerged regarding the plausible role of the gut microbiome in IMIDs. This study used 16S rRNA gene amplicon sequencing to compare the gut microbiota of patients with Crohn’s disease (CD; N = 20), ulcerative colitis (UC; N = 19), multiple sclerosis (MS; N = 19), and rheumatoid arthritis (RA; N = 21) versus healthy controls (HC; N = 23). Biological replicates were collected from participants within a 2-month interval. This study aimed to identify common (or unique) taxonomic biomarkers of IMIDs using both differential abundance testing and a machine learning approach. Results Significant microbial community differences between cohorts were observed (pseudo F = 4.56; p = 0.01). Richness and diversity were significantly different between cohorts (pFDR < 0.001) and were lowest in CD while highest in HC. Abundances of Actinomyces, Eggerthella, Clostridium III, Faecalicoccus, and Streptococcus (pFDR < 0.001) were significantly higher in all disease cohorts relative to HC, whereas significantly lower abundances were observed for Gemmiger, Lachnospira, and Sporobacter (pFDR < 0.001). Several taxa were found to be differentially abundant in IMIDs versus HC including significantly higher abundances of Intestinibacter in CD, Bifidobacterium in UC, and unclassified Erysipelotrichaceae in MS and significantly lower abundances of Coprococcus in CD, Dialister in MS, and Roseburia in RA. A machine learning approach to classify disease versus HC was highest for CD (AUC = 0.93 and AUC = 0.95 for OTU and genus features, respectively) followed by MS, RA, and UC. Gemmiger and Faecalicoccus were identified as important features for classification of subjects to CD and HC. In general, features identified by differential abundance testing were consistent with machine learning feature importance. Conclusions This study identified several gut microbial taxa with differential abundance patterns common to IMIDs. We also found differentially abundant taxa between IMIDs. These taxa may serve as biomarkers for the detection and diagnosis of IMIDs and suggest there may be a common component to IMID etiology.
Open Access
A comparison of biologically variable ventilation to recruitment manoeuvres in a porcine model of acute lung injury
(2004-11-24) Funk, Duane J; Graham, M R; Girling, Linda G; Thliveris, James A; McManus, Bruce M; Walker, Elizabeth K; Rector, Edward S; Hillier, Craig; Scott, J E; Mutch, W A C
Abstract Background Biologically variable ventilation (return of physiological variability in rate and tidal volume using a computer-controller) was compared to control mode ventilation with and without a recruitment manoeuvre – 40 cm H2O for 40 sec performed hourly; in a porcine oleic acid acute lung injury model. Methods We compared gas exchange, respiratory mechanics, and measured bronchoalveolar fluid for inflammatory cytokines, cell counts and surfactant function. Lung injury was scored by light microscopy. Pigs received mechanical ventilation (FIO2 = 0.3; PEEP 5 cm H2O) in control mode until PaO2 decreased to 60 mm Hg with oleic acid infusion (PaO2/FIO2 <200 mm Hg). Additional PEEP to 10 cm H2O was added after injury. Animals were randomized to one of the 3 modes of ventilation and followed for 5 hr after injury. Results PaO2 and respiratory system compliance was significantly greater with biologically variable ventilation compared to the other 2 groups. Mean and mean peak airway pressures were also lower. There were no differences in cell counts in bronchoalveolar fluid by flow cytometry, or interleukin-8 and -10 levels between groups. Lung injury scoring revealed no difference between groups in the regions examined. No differences in surfactant function were seen between groups by capillary surfactometry. Conclusions In this porcine model of acute lung injury, various indices to measure injury or inflammation did not differ between the 3 approaches to ventilation. However, when using a low tidal volume strategy with moderate levels of PEEP, sustained improvements in arterial oxygen tension and respiratory system compliance were only seen with BVV when compared to CMV or CMV with a recruitment manoeuvre.
Open Access
A Critical Review of Oxazolidinones: An Alternative or Replacement for Glycopeptides and Streptogramins?
(2001-1-1) Zhanel, George G; Schroeder, Coleen; Vercaigne, Lavern; Gin, Alfred S; Embil, John; Hoban, Daryl J
OBJECTIVE: To review the available data on the oxazolidinones linezolid and eperezolid.DATA SELECTION: Published reports were obtained by searching MEDLINE for articles published between 1992 and 2000, inclusive. References of published papers were also obtained and reviewed. Abstracts from scientific proceedings were reviewed.DATA EXTRACTION: Due to the limited data available regarding these agents, the criteria for study inclusion were not restrictive.DATA SYNTHESIS: The oxazolidinones (eg, linezolid) are a new antimicrobial class with a unique mechanism of action. They are active against resistant Gram-positive cocci including methicillin-susceptible and -resistant Staphylococcus aureus (MRSA), methicillin-susceptible and -resistant Staphylococccus epidermidis, vancomycin-resistant enterococci (VRE) and penicillin-resistant Streptococcus pneumoniae (PRSP). Linezolid is active against anaerobes and displays modest activity against fastidious Gram-negative pathogens such as Haemophilus influenzae, but is not active against Enterobacteriaceae. Linezolid is available both orally and parenterally, and has a bioavailability of 100%. Clinical trials comparing linezolid with standard therapy have demonstrated similar bacteriological and clinical cures rates to standard therapy in community- and hospital-acquired pneumonia, uncomplicated and complicated skin and soft tissue infections, and infections caused by MRSA and VRE. Adverse effects have been minor and infrequent; however, platelets should be monitored in patients who have received more than two weeks of linezolid therapy. It is expected that these agents will have a bright future due to their excellent spectrum of activity against antibiotic-resistant Gram-positive organisms, such as MRSA, VRE and PRSP, and their excellent bioavailability.CONCLUSION: The oxazolidinones represent a new class of antimicrobials with a unique mechanism of action. They have excellent activity against susceptible and resistant Gram-positive organisms such as MRSA, methicillin-susceptible S epidermidis, VRE and PRSP, and a good adverse effect profile; they can be administered both intravenously and orally. Their potential use in Canada may be as an intravenous and oral alternative to glycopeptides and streptogramins.
Open Access
A cross-sectional study evaluating cardiovascular risk and statin prescribing in the Canadian Primary Care Sentinel Surveillance Network database
(2022-05-25) Johnston, Ian S.; Miles, Brendan; Soos, Boglarka; Garies, Stephanie; Perez, Grace; Queenan, John A.; Drummond, Neil; Singer, Alexander
Abstract Background Cardiovascular disease (CVD) is a major cause of morbidity and mortality in Canada. Assessment and management of CVD risk is essential in reducing disease burden. This includes both clinical risk factors and socioeconomic factors, though few studies report on socioeconomic status in relation to CVD risk and treatment. The primary objective of this study was to estimate the cardiovascular risk of patients attending primary care practices across Canada; secondly, to evaluate concordance with care indicators suggested by current clinical practice guidelines for statin prescribing according to patients’ cardiovascular risk and socioeconomic status. Methods This cross-sectional observational study used the Canadian Primary Care Sentinel Surveillance Network (CPCSSN) database, which is comprised of clinical data from primary care electronic medical records. Patients aged 35-75y with at least one visit to their primary care provider between 2012 and 2016 were included. Patients were assigned to a CVD risk category (high, medium, low) and a deprivation quintile was calculated for those with full postal code available. Descriptive analyses were used to determine the proportion of patients in each risk category. Logistic regression was used to evaluate the consistency of statin prescribing according to national clinical guidelines by risk category and deprivation quintile. Results A total of 324,526 patients were included. Of those, 116,947 (36%) of patients were assigned to a high CVD risk category, primarily older adults, males, and those with co-morbidities. There were statistically significant differences between least (quintile 1) and most (quintile 5) deprived socioeconomic quintiles, with those at high CVD risk disproportionately in Q5 (odds ratio 1.4). Overall, 48% of high-risk patients had at least one statin prescription in their record. Patients in the lower socioeconomic groups had a higher risk of statin treatment which deviated from clinical guidelines. Conclusions Primary care patients who are at high CVD risk are more often male, older, have more co-morbidities and be assigned to more deprived SES quintiles, compared to those at low CVD risk. Additionally, patients who experience more challenging socioeconomic situations may be less likely to receive CVD treatment that is consistent with care guidelines.