Mark Loeb

McMaster University, Hamilton, Ontario, Canada

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Publications (229)1153.24 Total impact

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    ABSTRACT: Infection with mosquito-borne West Nile virus (WNV) is usually asymptomatic but can lead to severe WNV encephalitis. The innate cytokine, macrophage migration inhibitory factor (MIF), is elevated in patients with WNV encephalitis and promotes viral neuroinvasion and mortality in animal models. In a case-control study, we examined functional polymorphisms in the MIF locus in a cohort of 454 North American patients with neuroinvasive WNV disease and found patients homozygous for high-expression MIF alleles to be >20-fold ( p= 0.008) more likely to have WNV encephalitis. These data indicate that MIF is an important determinant of severity of WNV neuropathogenesis and may be a therapeutic target.
    No preview · Article · Feb 2016 · Cytokine
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    ABSTRACT: Based on a cohort of 966 patients, routine surveillance data were not sufficiently accurate for use in clinical trials investigating surgical site infections. Surveillance data can only be used if adequate 90-day follow-up is provided and if cases identified by surveillance are independently reviewed by a blinded outcome adjudication committee. Infect. Control Hosp. Epidemiol. 2016;1–3
    No preview · Article · Jan 2016 · Infection Control and Hospital Epidemiology
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    ABSTRACT: Monocyte phenotype and output changes with age, but why this occurs and how it impacts anti-bacterial immunity are not clear. We found that, in both humans and mice, circulating monocyte phenotype and function was altered with age due to increasing levels of TNF in the circulation that occur as part of the aging process. Ly6C+ monocytes from old (18-22 mo) mice and CD14+CD16+ intermediate/inflammatory monocytes from older adults also contributed to this "age-associated inflammation" as they produced more of the inflammatory cytokines IL6 and TNF in the steady state and when stimulated with bacterial products. Using an aged mouse model of pneumococcal colonization we found that chronic exposure to TNF with age altered the maturity of circulating monocytes, as measured by F4/80 expression, and this decrease in monocyte maturation was directly linked to susceptibility to infection. Ly6C+ monocytes from old mice had higher levels of CCR2 expression, which promoted premature egress from the bone marrow when challenged with Streptococcus pneumoniae. Although Ly6C+ monocyte recruitment and TNF levels in the blood and nasopharnyx were higher in old mice during S. pneumoniae colonization, bacterial clearance was impaired. Counterintuitively, elevated TNF and excessive monocyte recruitment in old mice contributed to impaired anti-pneumococcal immunity since bacterial clearance was improved upon pharmacological reduction of TNF or Ly6C+ monocytes, which were the major producers of TNF. Thus, with age TNF impairs inflammatory monocyte development, function and promotes premature egress, which contribute to systemic inflammation and is ultimately detrimental to anti-pneumococcal immunity.
    Full-text · Article · Jan 2016 · PLoS Pathogens
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    ABSTRACT: Background: Community-acquired pneumonia (CAP) is common and often severe. Purpose: To examine the effect of adjunctive corticosteroid therapy on mortality, morbidity, and duration of hospitalization in patients with CAP. Data Sources: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials through 24 May 2015. Study Selection: Randomized trials of systemic corticosteroids in hospitalized adults with CAP. Data Extraction: Two reviewers independently extracted study data and assessed risk of bias. Quality of evidence was assessed with the Grading of Recommendations Assessment, Development, and Evaluation system by consensus among the authors. Data Synthesis: The median age was typically in the 60s, and approximately 60% of patients were male. Adjunctive corticosteroids were associated with possible reductions in all-cause mortality (12 trials; 1974 patients; risk ratio [RR], 0.67 [95% CI, 0.45 to 1.01]; risk difference [RD], 2.8%; moderate certainty), need for mechanical ventilation (5 trials; 1060 patients; RR, 0.45 [CI, 0.26 to 0.79]; RD, 5.0%; moderate certainty), and the acute respiratory distress syndrome (4 trials; 945 patients; RR, 0.24 [CI, 0.10 to 0.56]; RD, 6.2%; moderate certainty). They also decreased time to clinical stability (5 trials; 1180 patients; mean difference,-1.22 days [CI, -2.08 to -0.35 days]; high certainty) and duration of hospitalization (6 trials; 1499 patients; mean difference, -1.00 day [CI, -1.79 to -0.21 days]; high certainty). Adjunctive corticosteroids increased frequency of hyperglycemia requiring treatment (6 trials; 1534 patients; RR, 1.49 [CI, 1.01 to 2.19]; RD, 3.5%; high certainty) but did not increase frequency of gastrointestinal hemorrhage. Limitations: There were few events and trials for many outcomes. Trials often excluded patients at high risk for adverse events. Conclusion: For hospitalized adults with CAP, systemic corticosteroid therapy may reduce mortality by approximately 3%, need for mechanical ventilation by approximately 5%, and hospital stay by approximately 1 day. Primary Funding Source: None.
    No preview · Article · Oct 2015 · Annals of internal medicine
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    ABSTRACT: Community-acquired pneumonia (CAP) is common and often severe. To examine the effect of adjunctive corticosteroid therapy on mortality, morbidity, and duration of hospitalization in patients with CAP. MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials through 24 May 2015. Randomized trials of systemic corticosteroids in hospitalized adults with CAP. Two reviewers independently extracted study data and assessed risk of bias. Quality of evidence was assessed with the Grading of Recommendations Assessment, Development and Evaluation system by consensus among the authors. The median age was typically in the 60s, and approximately 60% of patients were male. Adjunctive corticosteroids were associated with possible reductions in all-cause mortality (12 trials; 1974 patients; risk ratio [RR], 0.67 [95% CI, 0.45 to 1.01]; risk difference [RD], 2.8%; moderate certainty), need for mechanical ventilation (5 trials; 1060 patients; RR, 0.45 [CI, 0.26 to 0.79]; RD, 5.0%; moderate certainty), and the acute respiratory distress syndrome (4 trials; 945 patients; RR, 0.24 [CI, 0.10 to 0.56]; RD, 6.2%; moderate certainty). They also decreased time to clinical stability (5 trials; 1180 patients; mean difference, -1.22 days [CI, -2.08 to -0.35 days]; high certainty) and duration of hospitalization (6 trials; 1499 patients; mean difference, -1.00 day [CI, -1.79 to -0.21 days]; high certainty). Adjunctive corticosteroids increased frequency of hyperglycemia requiring treatment (6 trials; 1534 patients; RR, 1.49 [CI, 1.01 to 2.19]; RD, 3.5%; high certainty) but did not increase frequency of gastrointestinal hemorrhage. There were few events and trials for many outcomes. Trials often excluded patients at high risk for adverse events. For hospitalized adults with CAP, systemic corticosteroid therapy may reduce mortality by approximately 3%, need for mechanical ventilation by approximately 5%, and hospital stay by approximately 1 day. None.
    Full-text · Article · Aug 2015 · Annals of internal medicine
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    ABSTRACT: Children are key drivers of influenza transmission. Vaccinating school age children decreases influenza in the community. To pilot-test the methods for a future trial to compare the direct and indirect benefits of inactivated influenza vaccine (IIV) vs. live attenuated influenza vaccine (LAIV) in preventing influenza infection. During the 2013-14 influenza vaccination campaign, we piloted an open-label cluster randomized trial involving 10 elementary schools in Peterborough, Ontario, Canada. We randomized schools on a 1:1 basis to have students receive IIV or LAIV. We invited a subset of vaccinated students and their households to participate in a surveillance sub-study, which involved completing daily symptom diaries during influenza season and collecting mid-turbinate swabs from symptomatic individuals to detect influenza infection. The main outcome measure confirmed influenza infection using a real-time reverse transcriptase polymerase chain reaction (PCR) assay. One hundred and nineteen households (166 students and 293 household members) participated. During 15 weeks of surveillance, we detected 22 episodes of PCR-confirmed influenza (21 influenza A/H1N1 and 1 influenza B). The incidence of influenza per 1000 person-days was 1.24 (95% CI, 0.40-2.89) for IIV-vaccinated students, compared to 0.13 (95% CI, 0.003-0.72) for LAIV-vaccinated students; the incidence rate ratio was 0.10 (95% CI, 0.002-0.94). Similarly, the incidence of influenza per 1000 person-days was 1.33 (95% CI, 0.64-2.44) for IIV household members, compared to 0.47 (95% CI, 0.17-1.03) for LAIV household members; the incidence rate ratio was 0.36 (95% CI, 0.11-1.08). The overall incidence rate ratio (combining students and household members) was 0.27 (95% CI, 0.09-0.69). Household surveillance involving participant monitoring and reporting of symptoms and self-collection of mid-turbinate swabs is feasible. A larger study is required to validate the suggestion that vaccinating children with LAIV might confer more protection against influenza for both children and their household contacts, compared to IIV. ClinicalTrials.gov NCT01995851. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.
    Preview · Article · Jul 2015 · Vaccine
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    ABSTRACT: Although the microneutralization (MN) assay has been shown to be more sensitive than the hemagglutination inhibition (HAI) assay for the measurement of humoral immunity against influenza viruses, further evidence relating MN titres to protective efficacy against infection is needed. Serum antibodies against seasonal H1N1 and H3N2 influenza were measured in children and adolescents (n = 656) by MN and hemagglutination inhibition (HAI) assays. Compared to HAI, the MN assay is more sensitive in detecting serum antibodies and estimates of protective effectiveness against PCR-confirmed infection were higher for both subtypes. Given our findings, the MN assay warrants further consideration as a formal tool for the routine evaluation of vaccine-induced antibody responses.
    Full-text · Article · Jun 2015 · PLoS ONE
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    ABSTRACT: BACKGROUND: Increasing antimicrobial resistance has been identified as an important global health threat. Antimicrobial use is a major driver of resistance, especially in the hospital sector. Understanding the extent and type of antimicrobial use in Canadian hospitals will aid in developing national antimicrobial stewardship priorities. METHODS: In 2002 and 2009, as part of one-day prevalence surveys to quantify hospital-acquired infections in Canadian Nosocomial Infection Surveillance Program hospitals, data were collected on the use of systemic antimicrobial agents in all patients in participating hospitals. Specific agents in use (other than antiviral and antiparasitic agents) on the survey day and patient demographic information were collected. RESULTS: In 2002, 2460 of 6747 patients (36.5%) in 28 hospitals were receiving antimicrobial therapy. In 2009, 3989 of 9953 (40.1%) patients in 44 hospitals were receiving antimicrobial therapy (P<0.001). Significantly increased use was observed in central Canada (37.4% to 40.8%) and western Canada (36.9% to 41.1%) but not in eastern Canada (32.9% to 34.1%). In 2009, antimicrobial use was most common on solid organ transplant units (71.0% of patients), intensive care units (68.3%) and hematology/oncology units (65.9%). Compared with 2002, there was a significant decrease in use of firstand second-generation cephalosporins, and significant increases in use of carbapenems, antifungal agents and vancomycin in 2009. Piperacillin-tazobactam, as a proportion of all penicillins, increased from 20% in 2002 to 42.8% in 2009 (P<0.001). There was a significant increase in simultaneous use of >1 agent, from 12.0% of patients in 2002 to 37.7% in 2009. CONCLUSION: From 2002 to 2009, the prevalence of antimicrobial agent use in Canadian Nosocomial Infection Surveillance Program hospitals significantly increased; additionally, increased use of broadspectrum agents and a marked increase in simultaneous use of multiple agents were observed.
    Full-text · Article · Mar 2015
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    ABSTRACT: The 2014/15 influenza season in Canada has been characterised to date by early and intense activity dominated by influenza A(H3N2). A total of 99.0% (593/599) hospitalisations for laboratory-confirmed influenza with a known influenza virus type enrolled in sentinel hospitals of the Serious Outcomes Surveillance Network of the Canadian Immunization Research Network were due to influenza A. Of the 216 with a known subtype, influenza A(H3N2) accounted for 99.1% (n=214). Interim unmatched vaccine effectiveness (VE) estimates adjusted for age and presence of one or more medical comorbidities were determined by test-negative case-control design to be 16.8% (90% confidence interval (CI): -48.9 to 8.3) overall and -22.0% (90% CI: -66.5 to 10.7) for laboratory-confirmed influenza A(H3N2). Among adults aged under 65 years, the overall VE was 10.8% (90% CI: -50.2 to 47.0) while in adults aged 65 years or older, the overall VE was -25.4% (90% CI: -65.0 to 4.6).
    Full-text · Article · Feb 2015 · Eurosurveillance: bulletin europeen sur les maladies transmissibles = European communicable disease bulletin
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    ABSTRACT: Tumor necrosis factor (TNF), a potent inflammatory cytokine, and mitochondrial DNA (mtDNA), a product of inflammation-induced tissue damage, increase with age ("inflammaging") and many chronic diseases. Peripheral blood neutrophils, a critical component of innate immunity, have also been shown to be altered with age, and are exceptionally sensitive to external stimuli. Herein, we describe that the phenotype of neutrophils from the advanced-age, frail elderly (ELD) is determined by levels of circulating TNF and mtDNA. Neutrophils from ELD donors are morphologically immature, and have higher levels of intracellular reactive oxygen species (ROS) and expression of the activation markers CD11b and HLA-DR. The frequency of CD11b(++) neutrophils correlated with plasma TNF, and recombinant TNF elevated neutrophil CD11b ex vivo and in vivo. Furthermore, neutrophils from aged TNF-deficient mice expressed CD11b similar to young counterparts. The frequency of HLA-DR(+) neutrophils, on the other hand, positively correlated with circulating mtDNA, which increased neutrophil HLA-DR expression in a dose-dependent manner ex vivo. Cell-surface TLR-9 expression, however, was unaltered on neutrophils from ELD donors. In summary, we provide novel evidence that products of age-related inflammation modulate neutrophil phenotype in vivo. Given this, anti-inflammatory therapies may prove beneficial in improving neutrophil functionality in the elderly. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Full-text · Article · Feb 2015 · Molecular Immunology
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    ABSTRACT: School-based influenza immunization can effectively address accessibility barriers, but injected inactivated influenza vaccines (IIV) may not be acceptable to some children and parents in school settings. To better understand the feasibility of offering intranasal live attenuated influenza vaccines (LAIV) through schools, we assessed uptake, stakeholder acceptability, and cost of school-based delivery of LAIV compared to IIV. We piloted an open-label cluster randomized trial involving 10 elementary schools in Peterborough, Ontario during the 2013-2014 influenza vaccination campaign. Schools were randomized to having students receive IIV or LAIV at publicly-funded school-based clinics organized by the local public health department. We measured the percentage of students vaccinated with at least one dose of influenza vaccine at school. Stakeholder acceptability was evaluated through a questionnaire of parents and interviews of public health department personnel and school principals. We compared the costs per dose of vaccine administered, including staff time and costs of vaccines and supplies. Single-dose influenza vaccine uptake was higher for the five schools offering LAIV than for the five offering IIV (19.3% vs. 12.2%, p=0.02). Interviews with nine school principals and five public health department personnel suggested that the clinics ran smoothly with little disruption to school routines, and that LAIV was associated with increased efficiency and calmer children. All interviewees cited unfamiliarity with LAIV and the study recruitment package length as potential reasons for low uptake. The cost per vaccine dose administered was $38.67 for IIV and $43.50 for LAIV. Use of LAIV in school-based clinics was associated with increased vaccine uptake and the perception among immunizing staff of reduced child anxiety, but also slightly higher vaccine administration costs, compared to IIV. However, uptake was low for both groups. More effective strategies to promote influenza vaccines and to obtain parent consent may improve vaccine uptake. ClinicalTrials.gov NCT01995851. Public Health Agency of Canada/Canadian Institutes of Health Research Influenza Research Network. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.
    Full-text · Article · Dec 2014 · Vaccine
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    ABSTRACT: Objectives: Vaccinating healthy children is proposed as a strategy to produce a herd effect and protect vulnerable groups. The Hutterite Influenza Prevention Study investigated this strategy, comparing communities with or without childhood influenza immunization programs. There are costs associated with vaccination therefore there may be a trade-off between these costs and the benefits of avoiding influenza cases. This evaluation estimates the cost-effectiveness of immunizing only healthy children in preventing cases of influenza within entire communities. Methods: Effect data and resource utilization were collected during the trial. Cost data were collected from payer, literature and Internet sources. A two-stage bootstrap (TSB) with shrinkage correction was used to estimate average costs and effects. The incremental cost effectiveness ratio (ICER) and sample uncertainty around this estimate were calculated from the TSB results. Results: Mean costs per patient for the treatment and control arms were $69.07 and $32.66 (difference $36.41). Mean number of influenza cases for the treatment and control arms were 0.04 and 0.27 (difference 0.23). ICER was $164.12 ($28.38, $2767.75) per case of influenza averted. Conclusions: Immunizing healthy children for influenza is more costly, yet more effective than no immunization in preventing cases in the sample. At a cost of $164.12 to prevent a case of influenza, immunizing healthy children to protect all community members may be considered costeffective. Estimated results are conservative as the influenza season was mild and the sample population was healthy. In a more severe season with a less healthy population the ICER is expected to decrease.
    No preview · Article · Nov 2014 · International Journal of Technology Assessment in Health Care
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    ABSTRACT: The advanced-age, frail elderly are especially vulnerable to developing pneumococcal infection and disease. Macrophages are critical mediators in the defence against Streptococcus pneumoniae at the upper respiratory tract, however, little is known of their anti-pneumococcal capacity in the elderly. Herein we demonstrate that monocyte-derived macrophages (MDMs) from the advanced-age, frail elderly produce less TNF, IL-6, IL-1β and IL-8 in response to heat-killed S. pneumoniae, which does not appear to be related to mRNA stability or decay. Furthermore, despite maintaining the ability to bind and phagocytose bacteria, MDMs from these individuals have a reduced capacity to kill S. pneumoniae. These defects parallel reduced PI3K-AKT signaling, which can significantly abrogate bacterial killing, but does not affect cytokine responses. Since macrophages are critical in the defence against S. pneumoniae, this study adds valuable insight into the susceptibility of the elderly to pneumococcal disease and highlights the PI3K-AKT signaling pathway as a potential therapeutic target.
    No preview · Article · Oct 2014 · Human Immunology
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    ABSTRACT: Elevated levels of serum cytokines, a marker of immune activation and chronic inflammation, are commonly associated with age and are a significant risk factor for all-cause mortality in the elderly. This phenomenon is very similar to that exhibited by individuals with diseases of inflammatory etiology and chronic viral infections such as human immunodeficiency virus (HIV). Although the origin of chronically elevated cytokines with age is unknown, for chronic diseases and viral infections, a role for circulating bacterial products and other pattern recognition receptor (PRR) ligands has been suggested. Given this, we sought to examine whether the levels of circulating cytokines (tumour necrosis factor (TNF), interferon-gamma (IFN-γ), interleukin (IL)-1β, IL-6, IL-8, IL-10, IL-12) in the advanced-age, frail elderly (n = 135) correlated with plasma levels of lipopolysaccharide (LPS), muramyl dipeptide (MDP), 16S ribosomal DNA, total cell-free DNA and host-derived mitochondrial DNA. After adjusting for multiple testing, no associations between circulating products and donor age, sex or comorbidities were observed. However, a significant negative correlation between MDP and IL-10 was identified. Given the anti-inflammatory nature of IL-10, a negative relationship with a potent inflammatory agonist such as MDP is not surprising and suggests a potential role for circulating MDP in the propagation of age-related immune activation.
    Full-text · Article · Oct 2014 · Inflammation
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    ABSTRACT: Objective To determine if immune phenotypes associated with immunosenescence predict risk of respiratory viral infection in elderly nursing home residents. Methods Residents ≥65 years from 32 nursing homes in 4 Canadian cities were enrolled in Fall 2009, 2010 and 2011, and followed for one influenza season. Following influenza vaccination, peripheral blood mononuclear cells (PBMCs) were obtained and analysed by flow cytometry for T-regs, CD4+ and CD8+ T-cell subsets (CCR7+CD45RA+, CCR7-CD45RA+ and CD28-CD57+) and CMV-reactive CD4+ and CD8+ T-cells. Nasopharyngeal swabs were obtained and tested for viruses in symptomatic residents. A Cox proportional hazards model adjusted for age, sex and frailty, determined the relationship between immune phenotypes and time to viral infection. Results 1072 residents were enrolled; median age 86 years and 72% female. 269 swabs were obtained, 87 were positive for virus: influenza (24%), RSV (14%), coronavirus (32%), rhinovirus (17%), human metapneumovirus (9%) and parainfluenza (5%). In multivariable analysis, high T-reg% (HR 0.41, 95% CI 0.20–0.81) and high CMV-reactive CD4+ T-cell% (HR 1.69, 95% CI 1.03–2.78) were predictive of respiratory viral infection. Conclusions In elderly nursing home residents, high CMV-reactive CD4+ T-cells were associated with an increased risk and high T-regs were associated with a reduced risk of respiratory viral infection.
    Full-text · Article · Oct 2014 · PLoS ONE
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    ABSTRACT: Importance Infection management in advanced dementia has important implications for (1) providing high-quality care to patients near the end of life and (2) minimizing the public health threat posed by the emergence of multidrug-resistant organisms (MDROs).Design, Setting, and Participants Prospective cohort study of 362 residents with advanced dementia and their health care proxies in 35 Boston area nursing homes for up to 12 months.Main Outcomes and Measures Data were collected to characterize suspected infections, use of antimicrobial agents (antimicrobials), clinician counseling of proxies about antimicrobials, proxy preference for the goals of care, and colonization with MDROs (methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, and multidrug-resistant gram-negative bacteria). Main outcomes were (1) proportion of suspected infections treated with antimicrobials that met minimum clinical criteria to initiate antimicrobial treatment based on consensus guidelines and (2) cumulative incidence of MDRO acquisition among noncolonized residents at baseline.Results The cohort experienced 496 suspected infections; 72.4% were treated with antimicrobials, most commonly quinolones (39.8%) and third- or fourth-generation cephalosporins (20.6%). At baseline, 94.8% of proxies stated that comfort was the primary goal of care, and 37.8% received counseling from clinicians about antimicrobial use. Minimum clinical criteria supporting antimicrobial treatment initiation were present for 44.0% of treated episodes and were more likely when proxies were counseled about antimicrobial use (adjusted odds ratio, 1.42; 95% CI, 1.08-1.86) and when the infection source was not the urinary tract (referent). Among noncolonized residents at baseline, the cumulative incidence of MDRO acquisition at 1 year was 48%. Acquisition was associated with exposure (>1 day) to quinolones (adjusted hazard ratio [AHR], 1.89; 95% CI, 1.28-2.81) and third- or fourth-generation cephalosporins (AHR, 1.57; 95% CI, 1.04-2.40).Conclusions and Relevance Antimicrobials are prescribed for most suspected infections in advanced dementia but often in the absence of minimum clinical criteria to support their use. Colonization with MDROs is extensive in nursing homes and is associated with exposure to quinolones and third- and fourth-generation cephalosporins. A more judicious approach to infection management may reduce unnecessary treatment in these frail patients, who most often have comfort as their primary goal of care, and the public health threat of MDRO emergence.
    No preview · Article · Aug 2014 · JAMA Internal Medicine
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    ABSTRACT: Background Circulating myeloid cells are important mediators of the inflammatory response, acting as a major source of resident tissue antigen presenting cells and serum cytokines. They represent a number of distinct subpopulations whose functional capacity and relative concentrations are known to change with age. Little is known of these changes in the very old and physically frail, a rapidly increasing proportion of the North American population. Design In the following study the frequency and receptor expression of blood monocytes and dendritic cells (DCs) were characterized in a sample of advanced-age, frail elderly (81–100 yrs), and compared against that of adults (19–59 yrs), and community-dwelling seniors (61–76 yrs). Cytokine responses following TLR stimulation were also investigated, as well as associations between immunophenotyping parameters and chronic diseases. Results The advanced-age, frail elderly had significantly fewer CD14(++) and CD14(+)CD16(+), but not CD14(++)CD16(+) monocytes, fewer plasmacytoid and myeloid DCs, and a lower frequency of monocytes expressing the chemokine receptors CCR2 and CX3CR1. At baseline and following stimulation with TLR-2 and -4 agonists, monocytes from the advanced-age, frail elderly produced more TNF than adults, although the overall induction was significantly lower. Finally, monocyte subset frequency and CX3CR1 expression was positively associated with dementia, while negatively associated with anemia and diabetes in the advanced-age, frail elderly. Conclusions These data demonstrate that blood monocyte frequency and phenotype are altered in the advanced-age, frail elderly and that these changes correlate with certain chronic diseases. Whether these changes contribute to or are caused by these conditions warrants further investigation.
    Full-text · Article · Aug 2014 · PLoS ONE

  • No preview · Article · Aug 2014 · Survey of Anesthesiology
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    Preview · Article · Jul 2014 · Influenza and Other Respiratory Viruses
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    ABSTRACT: We undertook a 2X2 factorial, randomized controlled trial (RCT) to assess whether vitamin D3 supplementation (10,000 international units per week) versus placebo and gargling versus no gargling could prevent viral, clinical upper respiratory tract infection (URTI) in university students. We randomized 600 students into 4 treatment arms: 1) vitamin D3 and gargling, 2) placebo and gargling, 3) vitamin D3 and no gargling, and 4) placebo and no gargling. Students completed weekly electronic surveys and submitted self-collected mid-turbinate nasal flocked swabs during September and October in 2010 or 2011. Symptomatic students also completed an electronic symptom diary. The primary and secondary outcomes were the occurrence of symptomatic clinical URTI and laboratory confirmed URTI respectively. Of 600 participants, 471 (78.5%) completed all surveys while 43 (7.2%) completed none; 150 (25.0%) reported clinical URTI. Seventy participants (23.3%) randomized to vitamin D3 reported clinical URTI compared to 80 (26.7%) randomized to placebo (RR:0.79, CI95:0.61-1.03, p = 0.09). Eighty-five participants (28.3%) randomized to gargling reported clinical URTI compared to 65 participants (21.7%) randomized to the no gargling arm (RR:1.3, CI95:0.92-1.57, p = 0.19). Laboratory testing identified 70 infections (46.7 per 100 URTIs). Vitamin D3 treatment was associated with a significantly lower risk for laboratory confirmed URTI (RR: 0.54, CI95:0.34-0.84, p = 0.007) and with a significantly lower mean viral load measured as log10 viral copies/mL (mean difference: -0.89, CI95: -1.7, -0.06, p = 0.04). Fewer students assigned to gargling experienced laboratory confirmed URTI, however this was not statistically significant (RR:0.82, CI95:0.53-1.26, p = 0.36). These results suggest that vitamin D3 is a promising intervention for the prevention of URTI. Vitamin D3 significantly reduced the risk of laboratory confirmed URTI and may reduce the risk of clinical infections. Trial registration Clinical Trials Registration: NCT01158560.
    Full-text · Article · May 2014 · BMC Infectious Diseases

Publication Stats

6k Citations
1,153.24 Total Impact Points

Institutions

  • 1997-2016
    • McMaster University
      • • Department of Medicine
      • • Department of Clinical Epidemiology and Biostatistics
      • • Department of Pathology and Molecular Medicine
      • • Faculty of Health Sciences
      Hamilton, Ontario, Canada
  • 2015
    • University of Oslo
      Kristiania (historical), Oslo, Norway
  • 2012
    • Innlandet Hospital Trust
      Brumunddalen, Hedmark, Norway
  • 1998-2010
    • Hamilton Health Sciences
      Hamilton, Ontario, Canada
  • 2004-2008
    • Sunnybrook Health Sciences Centre
      • Division of Microbiology
      Toronto, Ontario, Canada
  • 2003-2007
    • Mount Sinai Hospital, Toronto
      • Department of Microbiology
      Toronto, Ontario, Canada
  • 2006
    • University Health Network
      • Division of Experimental Therapeutics
      Toronto, Ontario, Canada